Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia

Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. An...
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Autor*in:	Hope Mumme [verfasserIn] Beena E. Thomas [verfasserIn] Swati S. Bhasin [verfasserIn] Upaasana Krishnan [verfasserIn] Bhakti Dwivedi [verfasserIn] Pruthvi Perumalla [verfasserIn] Debasree Sarkar [verfasserIn] Gulay B. Ulukaya [verfasserIn] Himalee S. Sabnis [verfasserIn] Sunita I. Park [verfasserIn] Deborah DeRyckere [verfasserIn] Sunil S. Raikar [verfasserIn] Melinda Pauly [verfasserIn] Ryan J. Summers [verfasserIn] Sharon M. Castellino [verfasserIn] Daniel S. Wechsler [verfasserIn] Christopher C. Porter [verfasserIn] Douglas K. Graham [verfasserIn] Manoj Bhasin [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: Nature Communications - Nature Portfolio, 2016, 14(2023), 1, Seite 20
Übergeordnetes Werk:	volume:14 ; year:2023 ; number:1 ; pages:20

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41467-023-41994-0

Katalog-ID:	DOAJ092898122

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Indexfelder

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allfields	10.1038/s41467-023-41994-0 doi (DE-627)DOAJ092898122 (DE-599)DOAJa3787863b5cb43ff9dcb50ae8a436b4d DE-627 ger DE-627 rakwb eng Hope Mumme verfasserin aut Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape. Science Q Beena E. Thomas verfasserin aut Swati S. Bhasin verfasserin aut Upaasana Krishnan verfasserin aut Bhakti Dwivedi verfasserin aut Pruthvi Perumalla verfasserin aut Debasree Sarkar verfasserin aut Gulay B. Ulukaya verfasserin aut Himalee S. Sabnis verfasserin aut Sunita I. Park verfasserin aut Deborah DeRyckere verfasserin aut Sunil S. Raikar verfasserin aut Melinda Pauly verfasserin aut Ryan J. Summers verfasserin aut Sharon M. Castellino verfasserin aut Daniel S. Wechsler verfasserin aut Christopher C. Porter verfasserin aut Douglas K. Graham verfasserin aut Manoj Bhasin verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 20 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:20 https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d kostenfrei https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/toc/2041-1723 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 20
spelling	10.1038/s41467-023-41994-0 doi (DE-627)DOAJ092898122 (DE-599)DOAJa3787863b5cb43ff9dcb50ae8a436b4d DE-627 ger DE-627 rakwb eng Hope Mumme verfasserin aut Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape. Science Q Beena E. Thomas verfasserin aut Swati S. Bhasin verfasserin aut Upaasana Krishnan verfasserin aut Bhakti Dwivedi verfasserin aut Pruthvi Perumalla verfasserin aut Debasree Sarkar verfasserin aut Gulay B. Ulukaya verfasserin aut Himalee S. Sabnis verfasserin aut Sunita I. Park verfasserin aut Deborah DeRyckere verfasserin aut Sunil S. Raikar verfasserin aut Melinda Pauly verfasserin aut Ryan J. Summers verfasserin aut Sharon M. Castellino verfasserin aut Daniel S. Wechsler verfasserin aut Christopher C. Porter verfasserin aut Douglas K. Graham verfasserin aut Manoj Bhasin verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 20 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:20 https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d kostenfrei https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/toc/2041-1723 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 20
allfields_unstemmed	10.1038/s41467-023-41994-0 doi (DE-627)DOAJ092898122 (DE-599)DOAJa3787863b5cb43ff9dcb50ae8a436b4d DE-627 ger DE-627 rakwb eng Hope Mumme verfasserin aut Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape. Science Q Beena E. Thomas verfasserin aut Swati S. Bhasin verfasserin aut Upaasana Krishnan verfasserin aut Bhakti Dwivedi verfasserin aut Pruthvi Perumalla verfasserin aut Debasree Sarkar verfasserin aut Gulay B. Ulukaya verfasserin aut Himalee S. Sabnis verfasserin aut Sunita I. Park verfasserin aut Deborah DeRyckere verfasserin aut Sunil S. Raikar verfasserin aut Melinda Pauly verfasserin aut Ryan J. Summers verfasserin aut Sharon M. Castellino verfasserin aut Daniel S. Wechsler verfasserin aut Christopher C. Porter verfasserin aut Douglas K. Graham verfasserin aut Manoj Bhasin verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 20 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:20 https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d kostenfrei https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/toc/2041-1723 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 20
allfieldsGer	10.1038/s41467-023-41994-0 doi (DE-627)DOAJ092898122 (DE-599)DOAJa3787863b5cb43ff9dcb50ae8a436b4d DE-627 ger DE-627 rakwb eng Hope Mumme verfasserin aut Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape. Science Q Beena E. Thomas verfasserin aut Swati S. Bhasin verfasserin aut Upaasana Krishnan verfasserin aut Bhakti Dwivedi verfasserin aut Pruthvi Perumalla verfasserin aut Debasree Sarkar verfasserin aut Gulay B. Ulukaya verfasserin aut Himalee S. Sabnis verfasserin aut Sunita I. Park verfasserin aut Deborah DeRyckere verfasserin aut Sunil S. Raikar verfasserin aut Melinda Pauly verfasserin aut Ryan J. Summers verfasserin aut Sharon M. Castellino verfasserin aut Daniel S. Wechsler verfasserin aut Christopher C. Porter verfasserin aut Douglas K. Graham verfasserin aut Manoj Bhasin verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 20 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:20 https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d kostenfrei https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/toc/2041-1723 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 20
allfieldsSound	10.1038/s41467-023-41994-0 doi (DE-627)DOAJ092898122 (DE-599)DOAJa3787863b5cb43ff9dcb50ae8a436b4d DE-627 ger DE-627 rakwb eng Hope Mumme verfasserin aut Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape. Science Q Beena E. Thomas verfasserin aut Swati S. Bhasin verfasserin aut Upaasana Krishnan verfasserin aut Bhakti Dwivedi verfasserin aut Pruthvi Perumalla verfasserin aut Debasree Sarkar verfasserin aut Gulay B. Ulukaya verfasserin aut Himalee S. Sabnis verfasserin aut Sunita I. Park verfasserin aut Deborah DeRyckere verfasserin aut Sunil S. Raikar verfasserin aut Melinda Pauly verfasserin aut Ryan J. Summers verfasserin aut Sharon M. Castellino verfasserin aut Daniel S. Wechsler verfasserin aut Christopher C. Porter verfasserin aut Douglas K. Graham verfasserin aut Manoj Bhasin verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 20 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:20 https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d kostenfrei https://doi.org/10.1038/s41467-023-41994-0 kostenfrei https://doaj.org/toc/2041-1723 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 20
language	English
source	In Nature Communications 14(2023), 1, Seite 20 volume:14 year:2023 number:1 pages:20
sourceStr	In Nature Communications 14(2023), 1, Seite 20 volume:14 year:2023 number:1 pages:20
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container_title	Nature Communications
authorswithroles_txt_mv	Hope Mumme @@aut@@ Beena E. Thomas @@aut@@ Swati S. Bhasin @@aut@@ Upaasana Krishnan @@aut@@ Bhakti Dwivedi @@aut@@ Pruthvi Perumalla @@aut@@ Debasree Sarkar @@aut@@ Gulay B. Ulukaya @@aut@@ Himalee S. Sabnis @@aut@@ Sunita I. Park @@aut@@ Deborah DeRyckere @@aut@@ Sunil S. Raikar @@aut@@ Melinda Pauly @@aut@@ Ryan J. Summers @@aut@@ Sharon M. Castellino @@aut@@ Daniel S. Wechsler @@aut@@ Christopher C. Porter @@aut@@ Douglas K. Graham @@aut@@ Manoj Bhasin @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
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author	Hope Mumme
spellingShingle	Hope Mumme misc Science misc Q Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
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topic_title	Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
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title	Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
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title_full	Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
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author_browse	Hope Mumme Beena E. Thomas Swati S. Bhasin Upaasana Krishnan Bhakti Dwivedi Pruthvi Perumalla Debasree Sarkar Gulay B. Ulukaya Himalee S. Sabnis Sunita I. Park Deborah DeRyckere Sunil S. Raikar Melinda Pauly Ryan J. Summers Sharon M. Castellino Daniel S. Wechsler Christopher C. Porter Douglas K. Graham Manoj Bhasin
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title_sort	single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
title_auth	Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
abstract	Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.
abstractGer	Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.
abstract_unstemmed	Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.
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title_short	Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
url	https://doi.org/10.1038/s41467-023-41994-0 https://doaj.org/article/a3787863b5cb43ff9dcb50ae8a436b4d https://doaj.org/toc/2041-1723
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