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...
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In: Frontiers in Oncology - Frontiers Media S.A., 2012, 14(2024) |
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| Übergeordnetes Werk: |
volume:14 ; year:2024 |
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10.3389/fonc.2024.1337954 |
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DOAJ098716026 |
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| 245 | 1 | 0 | |a IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
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| 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 | |
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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 |
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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 |
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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 |
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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@@ |
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<?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. 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R - Medicine |
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Joaquin Garcia-Solorio |
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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 |
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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 |
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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 |
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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 |
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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 |
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IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
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IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia |
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Joaquin Garcia-Solorio |
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Frontiers in Oncology |
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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 |
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10.3389/fonc.2024.1337954 |
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verfasserin |
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ikzf1plus is a frequent biomarker of adverse prognosis in mexican pediatric patients with b-acute lymphoblastic leukemia |
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RC254-282 |
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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. |
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| 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 |
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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 |
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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 |
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10.3389/fonc.2024.1337954 |
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| score |
7.3993273 |