IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia
BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis...
Ausführliche Beschreibung
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2024 |
---|
Schlagwörter: |
---|
Übergeordnetes Werk: |
In: Frontiers in Oncology - Frontiers Media S.A., 2012, 14(2024) |
---|---|
Übergeordnetes Werk: |
volume:14 ; year:2024 |
Links: |
---|
DOI / URN: |
10.3389/fonc.2024.1337954 |
---|
Katalog-ID: |
DOAJ098716026 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | DOAJ098716026 | ||
003 | DE-627 | ||
005 | 20240414000153.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240414s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3389/fonc.2024.1337954 |2 doi | |
035 | |a (DE-627)DOAJ098716026 | ||
035 | |a (DE-599)DOAJ957fbd226ef74958b32478db98abf26c | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
050 | 0 | |a RC254-282 | |
100 | 0 | |a Joaquin Garcia-Solorio |e verfasserin |4 aut | |
245 | 1 | 0 | |a IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. | ||
650 | 4 | |a IKZF1plus | |
650 | 4 | |a IKZF1 gene mutation | |
650 | 4 | |a CDKN2A/2B gene mutation | |
650 | 4 | |a PAX5 gene mutation | |
650 | 4 | |a PAR1 deletions | |
650 | 4 | |a pediatric B-ALL | |
653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
700 | 0 | |a Juan Carlos Núñez-Enriquez |e verfasserin |4 aut | |
700 | 0 | |a Marco Jiménez-Olivares |e verfasserin |4 aut | |
700 | 0 | |a Janet Flores-Lujano |e verfasserin |4 aut | |
700 | 0 | |a Fernanda Flores-Espino |e verfasserin |4 aut | |
700 | 0 | |a Carolina Molina-Garay |e verfasserin |4 aut | |
700 | 0 | |a Alejandra Cervera |e verfasserin |4 aut | |
700 | 0 | |a Diana Casique-Aguirre |e verfasserin |4 aut | |
700 | 0 | |a Diana Casique-Aguirre |e verfasserin |4 aut | |
700 | 0 | |a José Gabriel Peñaloza-Gonzalez |e verfasserin |4 aut | |
700 | 0 | |a Ma. Del Rocío Baños-Lara |e verfasserin |4 aut | |
700 | 0 | |a Ángel García-Soto |e verfasserin |4 aut | |
700 | 0 | |a César Alejandro Galván-Díaz |e verfasserin |4 aut | |
700 | 0 | |a Alberto Olaya-Vargas |e verfasserin |4 aut | |
700 | 0 | |a Hilario Flores Aguilar |e verfasserin |4 aut | |
700 | 0 | |a Minerva Mata-Rocha |e verfasserin |4 aut | |
700 | 0 | |a Miguel Ángel Garrido-Hernández |e verfasserin |4 aut | |
700 | 0 | |a Juan Carlos Solís-Poblano |e verfasserin |4 aut | |
700 | 0 | |a Nuria Citlalli Luna-Silva |e verfasserin |4 aut | |
700 | 0 | |a Lena Sarahi Cano-Cuapio |e verfasserin |4 aut | |
700 | 0 | |a Pierre Mitchel Aristil-Chery |e verfasserin |4 aut | |
700 | 0 | |a Fernando Herrera-Quezada |e verfasserin |4 aut | |
700 | 0 | |a Karol Carrillo-Sanchez |e verfasserin |4 aut | |
700 | 0 | |a Anallely Muñoz-Rivas |e verfasserin |4 aut | |
700 | 0 | |a Luis Leonardo Flores-Lagunes |e verfasserin |4 aut | |
700 | 0 | |a Elvia Cristina Mendoza-Caamal |e verfasserin |4 aut | |
700 | 0 | |a Beatriz Eugenia Villegas-Torres |e verfasserin |4 aut | |
700 | 0 | |a Vincent González-Osnaya |e verfasserin |4 aut | |
700 | 0 | |a Elva Jiménez-Hernández |e verfasserin |4 aut | |
700 | 0 | |a José Refugio Torres-Nava |e verfasserin |4 aut | |
700 | 0 | |a Jorge Alfonso Martín-Trejo |e verfasserin |4 aut | |
700 | 0 | |a María de Lourdes Gutiérrez-Rivera |e verfasserin |4 aut | |
700 | 0 | |a Rosa Martha Espinosa-Elizondo |e verfasserin |4 aut | |
700 | 0 | |a Laura Elizabeth Merino-Pasaye |e verfasserin |4 aut | |
700 | 0 | |a María Luisa Pérez-Saldívar |e verfasserin |4 aut | |
700 | 0 | |a Silvia Jiménez-Morales |e verfasserin |4 aut | |
700 | 0 | |a Everardo Curiel-Quesada |e verfasserin |4 aut | |
700 | 0 | |a Haydeé Rosas-Vargas |e verfasserin |4 aut | |
700 | 0 | |a Juan Manuel Mejía-Arangure |e verfasserin |4 aut | |
700 | 0 | |a Juan Manuel Mejía-Arangure |e verfasserin |4 aut | |
700 | 0 | |a Carmen Alaez-Verson |e verfasserin |4 aut | |
773 | 0 | 8 | |i In |t Frontiers in Oncology |d Frontiers Media S.A., 2012 |g 14(2024) |w (DE-627)684965518 |w (DE-600)2649216-7 |x 2234943X |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2024 |
856 | 4 | 0 | |u https://doi.org/10.3389/fonc.2024.1337954 |z kostenfrei |
856 | 4 | 0 | |u https://doaj.org/article/957fbd226ef74958b32478db98abf26c |z kostenfrei |
856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/2234-943X |y Journal toc |z kostenfrei |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_DOAJ | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 14 |j 2024 |
author_variant |
j g s jgs j c n e jcne m j o mjo j f l jfl f f e ffe c m g cmg a c ac d c a dca d c a dca j g p g jgpg m d r b l mdrbl á g s ágs c a g d cagd a o v aov h f a hfa m m r mmr m á g h mágh j c s p jcsp n c l s ncls l s c c lscc p m a c pmac f h q fhq k c s kcs a m r amr l l f l llfl e c m c ecmc b e v t bevt v g o vgo e j h ejh j r t n jrtn j a m t jamt m d l g r mdlgr r m e e rmee l e m p lemp m l p s mlps s j m sjm e c q ecq h r v hrv j m m a jmma j m m a jmma c a v cav |
---|---|
matchkey_str |
article:2234943X:2024----::kfpuiarqetimreoavrergoiimxcneitiptetwtb |
hierarchy_sort_str |
2024 |
callnumber-subject-code |
RC |
publishDate |
2024 |
allfields |
10.3389/fonc.2024.1337954 doi (DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c DE-627 ger DE-627 rakwb eng RC254-282 Joaquin Garcia-Solorio verfasserin aut IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens Juan Carlos Núñez-Enriquez verfasserin aut Marco Jiménez-Olivares verfasserin aut Janet Flores-Lujano verfasserin aut Fernanda Flores-Espino verfasserin aut Carolina Molina-Garay verfasserin aut Alejandra Cervera verfasserin aut Diana Casique-Aguirre verfasserin aut Diana Casique-Aguirre verfasserin aut José Gabriel Peñaloza-Gonzalez verfasserin aut Ma. Del Rocío Baños-Lara verfasserin aut Ángel García-Soto verfasserin aut César Alejandro Galván-Díaz verfasserin aut Alberto Olaya-Vargas verfasserin aut Hilario Flores Aguilar verfasserin aut Minerva Mata-Rocha verfasserin aut Miguel Ángel Garrido-Hernández verfasserin aut Juan Carlos Solís-Poblano verfasserin aut Nuria Citlalli Luna-Silva verfasserin aut Lena Sarahi Cano-Cuapio verfasserin aut Pierre Mitchel Aristil-Chery verfasserin aut Fernando Herrera-Quezada verfasserin aut Karol Carrillo-Sanchez verfasserin aut Anallely Muñoz-Rivas verfasserin aut Luis Leonardo Flores-Lagunes verfasserin aut Elvia Cristina Mendoza-Caamal verfasserin aut Beatriz Eugenia Villegas-Torres verfasserin aut Vincent González-Osnaya verfasserin aut Elva Jiménez-Hernández verfasserin aut José Refugio Torres-Nava verfasserin aut Jorge Alfonso Martín-Trejo verfasserin aut María de Lourdes Gutiérrez-Rivera verfasserin aut Rosa Martha Espinosa-Elizondo verfasserin aut Laura Elizabeth Merino-Pasaye verfasserin aut María Luisa Pérez-Saldívar verfasserin aut Silvia Jiménez-Morales verfasserin aut Everardo Curiel-Quesada verfasserin aut Haydeé Rosas-Vargas verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Carmen Alaez-Verson verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 14(2024) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:14 year:2024 https://doi.org/10.3389/fonc.2024.1337954 kostenfrei https://doaj.org/article/957fbd226ef74958b32478db98abf26c kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2024 |
spelling |
10.3389/fonc.2024.1337954 doi (DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c DE-627 ger DE-627 rakwb eng RC254-282 Joaquin Garcia-Solorio verfasserin aut IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens Juan Carlos Núñez-Enriquez verfasserin aut Marco Jiménez-Olivares verfasserin aut Janet Flores-Lujano verfasserin aut Fernanda Flores-Espino verfasserin aut Carolina Molina-Garay verfasserin aut Alejandra Cervera verfasserin aut Diana Casique-Aguirre verfasserin aut Diana Casique-Aguirre verfasserin aut José Gabriel Peñaloza-Gonzalez verfasserin aut Ma. Del Rocío Baños-Lara verfasserin aut Ángel García-Soto verfasserin aut César Alejandro Galván-Díaz verfasserin aut Alberto Olaya-Vargas verfasserin aut Hilario Flores Aguilar verfasserin aut Minerva Mata-Rocha verfasserin aut Miguel Ángel Garrido-Hernández verfasserin aut Juan Carlos Solís-Poblano verfasserin aut Nuria Citlalli Luna-Silva verfasserin aut Lena Sarahi Cano-Cuapio verfasserin aut Pierre Mitchel Aristil-Chery verfasserin aut Fernando Herrera-Quezada verfasserin aut Karol Carrillo-Sanchez verfasserin aut Anallely Muñoz-Rivas verfasserin aut Luis Leonardo Flores-Lagunes verfasserin aut Elvia Cristina Mendoza-Caamal verfasserin aut Beatriz Eugenia Villegas-Torres verfasserin aut Vincent González-Osnaya verfasserin aut Elva Jiménez-Hernández verfasserin aut José Refugio Torres-Nava verfasserin aut Jorge Alfonso Martín-Trejo verfasserin aut María de Lourdes Gutiérrez-Rivera verfasserin aut Rosa Martha Espinosa-Elizondo verfasserin aut Laura Elizabeth Merino-Pasaye verfasserin aut María Luisa Pérez-Saldívar verfasserin aut Silvia Jiménez-Morales verfasserin aut Everardo Curiel-Quesada verfasserin aut Haydeé Rosas-Vargas verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Carmen Alaez-Verson verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 14(2024) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:14 year:2024 https://doi.org/10.3389/fonc.2024.1337954 kostenfrei https://doaj.org/article/957fbd226ef74958b32478db98abf26c kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2024 |
allfields_unstemmed |
10.3389/fonc.2024.1337954 doi (DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c DE-627 ger DE-627 rakwb eng RC254-282 Joaquin Garcia-Solorio verfasserin aut IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens Juan Carlos Núñez-Enriquez verfasserin aut Marco Jiménez-Olivares verfasserin aut Janet Flores-Lujano verfasserin aut Fernanda Flores-Espino verfasserin aut Carolina Molina-Garay verfasserin aut Alejandra Cervera verfasserin aut Diana Casique-Aguirre verfasserin aut Diana Casique-Aguirre verfasserin aut José Gabriel Peñaloza-Gonzalez verfasserin aut Ma. Del Rocío Baños-Lara verfasserin aut Ángel García-Soto verfasserin aut César Alejandro Galván-Díaz verfasserin aut Alberto Olaya-Vargas verfasserin aut Hilario Flores Aguilar verfasserin aut Minerva Mata-Rocha verfasserin aut Miguel Ángel Garrido-Hernández verfasserin aut Juan Carlos Solís-Poblano verfasserin aut Nuria Citlalli Luna-Silva verfasserin aut Lena Sarahi Cano-Cuapio verfasserin aut Pierre Mitchel Aristil-Chery verfasserin aut Fernando Herrera-Quezada verfasserin aut Karol Carrillo-Sanchez verfasserin aut Anallely Muñoz-Rivas verfasserin aut Luis Leonardo Flores-Lagunes verfasserin aut Elvia Cristina Mendoza-Caamal verfasserin aut Beatriz Eugenia Villegas-Torres verfasserin aut Vincent González-Osnaya verfasserin aut Elva Jiménez-Hernández verfasserin aut José Refugio Torres-Nava verfasserin aut Jorge Alfonso Martín-Trejo verfasserin aut María de Lourdes Gutiérrez-Rivera verfasserin aut Rosa Martha Espinosa-Elizondo verfasserin aut Laura Elizabeth Merino-Pasaye verfasserin aut María Luisa Pérez-Saldívar verfasserin aut Silvia Jiménez-Morales verfasserin aut Everardo Curiel-Quesada verfasserin aut Haydeé Rosas-Vargas verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Carmen Alaez-Verson verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 14(2024) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:14 year:2024 https://doi.org/10.3389/fonc.2024.1337954 kostenfrei https://doaj.org/article/957fbd226ef74958b32478db98abf26c kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2024 |
allfieldsGer |
10.3389/fonc.2024.1337954 doi (DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c DE-627 ger DE-627 rakwb eng RC254-282 Joaquin Garcia-Solorio verfasserin aut IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens Juan Carlos Núñez-Enriquez verfasserin aut Marco Jiménez-Olivares verfasserin aut Janet Flores-Lujano verfasserin aut Fernanda Flores-Espino verfasserin aut Carolina Molina-Garay verfasserin aut Alejandra Cervera verfasserin aut Diana Casique-Aguirre verfasserin aut Diana Casique-Aguirre verfasserin aut José Gabriel Peñaloza-Gonzalez verfasserin aut Ma. Del Rocío Baños-Lara verfasserin aut Ángel García-Soto verfasserin aut César Alejandro Galván-Díaz verfasserin aut Alberto Olaya-Vargas verfasserin aut Hilario Flores Aguilar verfasserin aut Minerva Mata-Rocha verfasserin aut Miguel Ángel Garrido-Hernández verfasserin aut Juan Carlos Solís-Poblano verfasserin aut Nuria Citlalli Luna-Silva verfasserin aut Lena Sarahi Cano-Cuapio verfasserin aut Pierre Mitchel Aristil-Chery verfasserin aut Fernando Herrera-Quezada verfasserin aut Karol Carrillo-Sanchez verfasserin aut Anallely Muñoz-Rivas verfasserin aut Luis Leonardo Flores-Lagunes verfasserin aut Elvia Cristina Mendoza-Caamal verfasserin aut Beatriz Eugenia Villegas-Torres verfasserin aut Vincent González-Osnaya verfasserin aut Elva Jiménez-Hernández verfasserin aut José Refugio Torres-Nava verfasserin aut Jorge Alfonso Martín-Trejo verfasserin aut María de Lourdes Gutiérrez-Rivera verfasserin aut Rosa Martha Espinosa-Elizondo verfasserin aut Laura Elizabeth Merino-Pasaye verfasserin aut María Luisa Pérez-Saldívar verfasserin aut Silvia Jiménez-Morales verfasserin aut Everardo Curiel-Quesada verfasserin aut Haydeé Rosas-Vargas verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Carmen Alaez-Verson verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 14(2024) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:14 year:2024 https://doi.org/10.3389/fonc.2024.1337954 kostenfrei https://doaj.org/article/957fbd226ef74958b32478db98abf26c kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2024 |
allfieldsSound |
10.3389/fonc.2024.1337954 doi (DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c DE-627 ger DE-627 rakwb eng RC254-282 Joaquin Garcia-Solorio verfasserin aut IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens Juan Carlos Núñez-Enriquez verfasserin aut Marco Jiménez-Olivares verfasserin aut Janet Flores-Lujano verfasserin aut Fernanda Flores-Espino verfasserin aut Carolina Molina-Garay verfasserin aut Alejandra Cervera verfasserin aut Diana Casique-Aguirre verfasserin aut Diana Casique-Aguirre verfasserin aut José Gabriel Peñaloza-Gonzalez verfasserin aut Ma. Del Rocío Baños-Lara verfasserin aut Ángel García-Soto verfasserin aut César Alejandro Galván-Díaz verfasserin aut Alberto Olaya-Vargas verfasserin aut Hilario Flores Aguilar verfasserin aut Minerva Mata-Rocha verfasserin aut Miguel Ángel Garrido-Hernández verfasserin aut Juan Carlos Solís-Poblano verfasserin aut Nuria Citlalli Luna-Silva verfasserin aut Lena Sarahi Cano-Cuapio verfasserin aut Pierre Mitchel Aristil-Chery verfasserin aut Fernando Herrera-Quezada verfasserin aut Karol Carrillo-Sanchez verfasserin aut Anallely Muñoz-Rivas verfasserin aut Luis Leonardo Flores-Lagunes verfasserin aut Elvia Cristina Mendoza-Caamal verfasserin aut Beatriz Eugenia Villegas-Torres verfasserin aut Vincent González-Osnaya verfasserin aut Elva Jiménez-Hernández verfasserin aut José Refugio Torres-Nava verfasserin aut Jorge Alfonso Martín-Trejo verfasserin aut María de Lourdes Gutiérrez-Rivera verfasserin aut Rosa Martha Espinosa-Elizondo verfasserin aut Laura Elizabeth Merino-Pasaye verfasserin aut María Luisa Pérez-Saldívar verfasserin aut Silvia Jiménez-Morales verfasserin aut Everardo Curiel-Quesada verfasserin aut Haydeé Rosas-Vargas verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Juan Manuel Mejía-Arangure verfasserin aut Carmen Alaez-Verson verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 14(2024) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:14 year:2024 https://doi.org/10.3389/fonc.2024.1337954 kostenfrei https://doaj.org/article/957fbd226ef74958b32478db98abf26c kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2024 |
language |
English |
source |
In Frontiers in Oncology 14(2024) volume:14 year:2024 |
sourceStr |
In Frontiers in Oncology 14(2024) volume:14 year:2024 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
isfreeaccess_bool |
true |
container_title |
Frontiers in Oncology |
authorswithroles_txt_mv |
Joaquin Garcia-Solorio @@aut@@ Juan Carlos Núñez-Enriquez @@aut@@ Marco Jiménez-Olivares @@aut@@ Janet Flores-Lujano @@aut@@ Fernanda Flores-Espino @@aut@@ Carolina Molina-Garay @@aut@@ Alejandra Cervera @@aut@@ Diana Casique-Aguirre @@aut@@ José Gabriel Peñaloza-Gonzalez @@aut@@ Ma. Del Rocío Baños-Lara @@aut@@ Ángel García-Soto @@aut@@ César Alejandro Galván-Díaz @@aut@@ Alberto Olaya-Vargas @@aut@@ Hilario Flores Aguilar @@aut@@ Minerva Mata-Rocha @@aut@@ Miguel Ángel Garrido-Hernández @@aut@@ Juan Carlos Solís-Poblano @@aut@@ Nuria Citlalli Luna-Silva @@aut@@ Lena Sarahi Cano-Cuapio @@aut@@ Pierre Mitchel Aristil-Chery @@aut@@ Fernando Herrera-Quezada @@aut@@ Karol Carrillo-Sanchez @@aut@@ Anallely Muñoz-Rivas @@aut@@ Luis Leonardo Flores-Lagunes @@aut@@ Elvia Cristina Mendoza-Caamal @@aut@@ Beatriz Eugenia Villegas-Torres @@aut@@ Vincent González-Osnaya @@aut@@ Elva Jiménez-Hernández @@aut@@ José Refugio Torres-Nava @@aut@@ Jorge Alfonso Martín-Trejo @@aut@@ María de Lourdes Gutiérrez-Rivera @@aut@@ Rosa Martha Espinosa-Elizondo @@aut@@ Laura Elizabeth Merino-Pasaye @@aut@@ María Luisa Pérez-Saldívar @@aut@@ Silvia Jiménez-Morales @@aut@@ Everardo Curiel-Quesada @@aut@@ Haydeé Rosas-Vargas @@aut@@ Juan Manuel Mejía-Arangure @@aut@@ Carmen Alaez-Verson @@aut@@ |
publishDateDaySort_date |
2024-01-01T00:00:00Z |
hierarchy_top_id |
684965518 |
id |
DOAJ098716026 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ098716026</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414000153.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fonc.2024.1337954</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ098716026</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ957fbd226ef74958b32478db98abf26c</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC254-282</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Joaquin Garcia-Solorio</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, &gt;50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IKZF1plus</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IKZF1 gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CDKN2A/2B gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PAX5 gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PAR1 deletions</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pediatric B-ALL</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Carlos Núñez-Enriquez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marco Jiménez-Olivares</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Janet Flores-Lujano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernanda Flores-Espino</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carolina Molina-Garay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alejandra Cervera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diana Casique-Aguirre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diana Casique-Aguirre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">José Gabriel Peñaloza-Gonzalez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ma. Del Rocío Baños-Lara</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ángel García-Soto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">César Alejandro Galván-Díaz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alberto Olaya-Vargas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hilario Flores Aguilar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Minerva Mata-Rocha</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Miguel Ángel Garrido-Hernández</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Carlos Solís-Poblano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nuria Citlalli Luna-Silva</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lena Sarahi Cano-Cuapio</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre Mitchel Aristil-Chery</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernando Herrera-Quezada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Karol Carrillo-Sanchez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anallely Muñoz-Rivas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis Leonardo Flores-Lagunes</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elvia Cristina Mendoza-Caamal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Beatriz Eugenia Villegas-Torres</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vincent González-Osnaya</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elva Jiménez-Hernández</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">José Refugio Torres-Nava</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jorge Alfonso Martín-Trejo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">María de Lourdes Gutiérrez-Rivera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rosa Martha Espinosa-Elizondo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura Elizabeth Merino-Pasaye</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">María Luisa Pérez-Saldívar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Silvia Jiménez-Morales</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Everardo Curiel-Quesada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Haydeé Rosas-Vargas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Manuel Mejía-Arangure</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Manuel Mejía-Arangure</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carmen Alaez-Verson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Oncology</subfield><subfield code="d">Frontiers Media S.A., 2012</subfield><subfield code="g">14(2024)</subfield><subfield code="w">(DE-627)684965518</subfield><subfield code="w">(DE-600)2649216-7</subfield><subfield code="x">2234943X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:14</subfield><subfield code="g">year:2024</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fonc.2024.1337954</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/957fbd226ef74958b32478db98abf26c</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2234-943X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">14</subfield><subfield code="j">2024</subfield></datafield></record></collection>
|
callnumber-first |
R - Medicine |
author |
Joaquin Garcia-Solorio |
spellingShingle |
Joaquin Garcia-Solorio misc RC254-282 misc IKZF1plus misc IKZF1 gene mutation misc CDKN2A/2B gene mutation misc PAX5 gene mutation misc PAR1 deletions misc pediatric B-ALL misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
authorStr |
Joaquin Garcia-Solorio |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)684965518 |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
DOAJ |
remote_str |
true |
callnumber-label |
RC254-282 |
illustrated |
Not Illustrated |
issn |
2234943X |
topic_title |
RC254-282 IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia IKZF1plus IKZF1 gene mutation CDKN2A/2B gene mutation PAX5 gene mutation PAR1 deletions pediatric B-ALL |
topic |
misc RC254-282 misc IKZF1plus misc IKZF1 gene mutation misc CDKN2A/2B gene mutation misc PAX5 gene mutation misc PAR1 deletions misc pediatric B-ALL misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
topic_unstemmed |
misc RC254-282 misc IKZF1plus misc IKZF1 gene mutation misc CDKN2A/2B gene mutation misc PAX5 gene mutation misc PAR1 deletions misc pediatric B-ALL misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
topic_browse |
misc RC254-282 misc IKZF1plus misc IKZF1 gene mutation misc CDKN2A/2B gene mutation misc PAX5 gene mutation misc PAR1 deletions misc pediatric B-ALL misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Frontiers in Oncology |
hierarchy_parent_id |
684965518 |
hierarchy_top_title |
Frontiers in Oncology |
isfreeaccess_txt |
true |
familylinks_str_mv |
(DE-627)684965518 (DE-600)2649216-7 |
title |
IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
ctrlnum |
(DE-627)DOAJ098716026 (DE-599)DOAJ957fbd226ef74958b32478db98abf26c |
title_full |
IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
author_sort |
Joaquin Garcia-Solorio |
journal |
Frontiers in Oncology |
journalStr |
Frontiers in Oncology |
callnumber-first-code |
R |
lang_code |
eng |
isOA_bool |
true |
recordtype |
marc |
publishDateSort |
2024 |
contenttype_str_mv |
txt |
author_browse |
Joaquin Garcia-Solorio Juan Carlos Núñez-Enriquez Marco Jiménez-Olivares Janet Flores-Lujano Fernanda Flores-Espino Carolina Molina-Garay Alejandra Cervera Diana Casique-Aguirre José Gabriel Peñaloza-Gonzalez Ma. Del Rocío Baños-Lara Ángel García-Soto César Alejandro Galván-Díaz Alberto Olaya-Vargas Hilario Flores Aguilar Minerva Mata-Rocha Miguel Ángel Garrido-Hernández Juan Carlos Solís-Poblano Nuria Citlalli Luna-Silva Lena Sarahi Cano-Cuapio Pierre Mitchel Aristil-Chery Fernando Herrera-Quezada Karol Carrillo-Sanchez Anallely Muñoz-Rivas Luis Leonardo Flores-Lagunes Elvia Cristina Mendoza-Caamal Beatriz Eugenia Villegas-Torres Vincent González-Osnaya Elva Jiménez-Hernández José Refugio Torres-Nava Jorge Alfonso Martín-Trejo María de Lourdes Gutiérrez-Rivera Rosa Martha Espinosa-Elizondo Laura Elizabeth Merino-Pasaye María Luisa Pérez-Saldívar Silvia Jiménez-Morales Everardo Curiel-Quesada Haydeé Rosas-Vargas Juan Manuel Mejía-Arangure Carmen Alaez-Verson |
container_volume |
14 |
class |
RC254-282 |
format_se |
Elektronische Aufsätze |
author-letter |
Joaquin Garcia-Solorio |
doi_str_mv |
10.3389/fonc.2024.1337954 |
author2-role |
verfasserin |
title_sort |
ikzf1plus is a frequent biomarker of adverse prognosis in mexican pediatric patients with b-acute lymphoblastic leukemia |
callnumber |
RC254-282 |
title_auth |
IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
abstract |
BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. |
abstractGer |
BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. |
abstract_unstemmed |
BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
title_short |
IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
url |
https://doi.org/10.3389/fonc.2024.1337954 https://doaj.org/article/957fbd226ef74958b32478db98abf26c https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full https://doaj.org/toc/2234-943X |
remote_bool |
true |
author2 |
Juan Carlos Núñez-Enriquez Marco Jiménez-Olivares Janet Flores-Lujano Fernanda Flores-Espino Carolina Molina-Garay Alejandra Cervera Diana Casique-Aguirre José Gabriel Peñaloza-Gonzalez Ma. Del Rocío Baños-Lara Ángel García-Soto César Alejandro Galván-Díaz Alberto Olaya-Vargas Hilario Flores Aguilar Minerva Mata-Rocha Miguel Ángel Garrido-Hernández Juan Carlos Solís-Poblano Nuria Citlalli Luna-Silva Lena Sarahi Cano-Cuapio Pierre Mitchel Aristil-Chery Fernando Herrera-Quezada Karol Carrillo-Sanchez Anallely Muñoz-Rivas Luis Leonardo Flores-Lagunes Elvia Cristina Mendoza-Caamal Beatriz Eugenia Villegas-Torres Vincent González-Osnaya Elva Jiménez-Hernández José Refugio Torres-Nava Jorge Alfonso Martín-Trejo María de Lourdes Gutiérrez-Rivera Rosa Martha Espinosa-Elizondo Laura Elizabeth Merino-Pasaye María Luisa Pérez-Saldívar Silvia Jiménez-Morales Everardo Curiel-Quesada Haydeé Rosas-Vargas Juan Manuel Mejía-Arangure Carmen Alaez-Verson |
author2Str |
Juan Carlos Núñez-Enriquez Marco Jiménez-Olivares Janet Flores-Lujano Fernanda Flores-Espino Carolina Molina-Garay Alejandra Cervera Diana Casique-Aguirre José Gabriel Peñaloza-Gonzalez Ma. Del Rocío Baños-Lara Ángel García-Soto César Alejandro Galván-Díaz Alberto Olaya-Vargas Hilario Flores Aguilar Minerva Mata-Rocha Miguel Ángel Garrido-Hernández Juan Carlos Solís-Poblano Nuria Citlalli Luna-Silva Lena Sarahi Cano-Cuapio Pierre Mitchel Aristil-Chery Fernando Herrera-Quezada Karol Carrillo-Sanchez Anallely Muñoz-Rivas Luis Leonardo Flores-Lagunes Elvia Cristina Mendoza-Caamal Beatriz Eugenia Villegas-Torres Vincent González-Osnaya Elva Jiménez-Hernández José Refugio Torres-Nava Jorge Alfonso Martín-Trejo María de Lourdes Gutiérrez-Rivera Rosa Martha Espinosa-Elizondo Laura Elizabeth Merino-Pasaye María Luisa Pérez-Saldívar Silvia Jiménez-Morales Everardo Curiel-Quesada Haydeé Rosas-Vargas Juan Manuel Mejía-Arangure Carmen Alaez-Verson |
ppnlink |
684965518 |
callnumber-subject |
RC - Internal Medicine |
mediatype_str_mv |
c |
isOA_txt |
true |
hochschulschrift_bool |
false |
doi_str |
10.3389/fonc.2024.1337954 |
callnumber-a |
RC254-282 |
up_date |
2024-07-03T18:47:57.185Z |
_version_ |
1803584774808272896 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ098716026</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414000153.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fonc.2024.1337954</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ098716026</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ957fbd226ef74958b32478db98abf26c</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC254-282</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Joaquin Garcia-Solorio</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, &gt;50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IKZF1plus</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IKZF1 gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CDKN2A/2B gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PAX5 gene mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PAR1 deletions</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pediatric B-ALL</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Carlos Núñez-Enriquez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marco Jiménez-Olivares</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Janet Flores-Lujano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernanda Flores-Espino</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carolina Molina-Garay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alejandra Cervera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diana Casique-Aguirre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diana Casique-Aguirre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">José Gabriel Peñaloza-Gonzalez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ma. Del Rocío Baños-Lara</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ángel García-Soto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">César Alejandro Galván-Díaz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alberto Olaya-Vargas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hilario Flores Aguilar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Minerva Mata-Rocha</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Miguel Ángel Garrido-Hernández</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Carlos Solís-Poblano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nuria Citlalli Luna-Silva</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lena Sarahi Cano-Cuapio</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre Mitchel Aristil-Chery</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernando Herrera-Quezada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Karol Carrillo-Sanchez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anallely Muñoz-Rivas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis Leonardo Flores-Lagunes</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elvia Cristina Mendoza-Caamal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Beatriz Eugenia Villegas-Torres</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vincent González-Osnaya</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elva Jiménez-Hernández</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">José Refugio Torres-Nava</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jorge Alfonso Martín-Trejo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">María de Lourdes Gutiérrez-Rivera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rosa Martha Espinosa-Elizondo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura Elizabeth Merino-Pasaye</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">María Luisa Pérez-Saldívar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Silvia Jiménez-Morales</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Everardo Curiel-Quesada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Haydeé Rosas-Vargas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Manuel Mejía-Arangure</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan Manuel Mejía-Arangure</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carmen Alaez-Verson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Oncology</subfield><subfield code="d">Frontiers Media S.A., 2012</subfield><subfield code="g">14(2024)</subfield><subfield code="w">(DE-627)684965518</subfield><subfield code="w">(DE-600)2649216-7</subfield><subfield code="x">2234943X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:14</subfield><subfield code="g">year:2024</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fonc.2024.1337954</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/957fbd226ef74958b32478db98abf26c</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fonc.2024.1337954/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2234-943X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">14</subfield><subfield code="j">2024</subfield></datafield></record></collection>
|
score |
7.3993273 |