Integrative Genomic Analysis of Pediatric Myeloid-Related Acute
Leukemias Identifies Novel Subtypes and Prognostic Indicators

J 2021

Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators

FORNEROD, M., J. MA, S. NOORT, Y. LIU, M. P. WALSH et. al.

Basic information

Original name

Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators

Authors

FORNEROD, M., J. MA, S. NOORT, Y. LIU, M. P. WALSH, L. SHI, S. NANCE, Y. L. LIU, Y. Y. WANG, G. C. SONG, T. LAMPRECHT, J. EASTON, H. L. MULDER, D. YERGEAU, J. MYERS, J. L. KAMENS, E. A. OBENG, M. PIGAZZI, Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), C. KELAIDI, S. POLYCHRONOPOULOU, J. K. LAMBA, S. D. BAKER, J. E. RUBNITZ, D. REINHARDT, M. M. VAN DEN HEUVEL-EIBRINK, F. LOCATELLI, H. HASLE, J. M. KLCO, J. R. DOWNING, J. H. ZHANG, S. POUNDS, C. M. ZWAAN and T. A. GRUBER

Edition

BLOOD CANCER DISCOVERY, PHILADELPHIA, AMER ASSOC CANCER RESEARCH, 2021, 2643-3230

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14110/21:00123864

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1158/2643-3230.BCD-21-0049

UT WoS

000715262200007

Keywords in English

Pediatric Myeloid-Related Acute Leukemias; Prognostic Indicators; Integrative Genomic Analysis

Abstract

V originále

Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell-like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification. SIGNIFICANCE: Immunophenotype and somatic mutations play a significant role in treatment approach and risk stratification of acute leukemia. We conducted an integrated genomic analysis of pediatric myeloid malignancies and found that a combination of genetic and transcriptional readouts was superior to immunophenotype and genomic mutations in identifying biological subtypes and predicting outcomes.

Citovat

FORNEROD, M., J. MA, S. NOORT, Y. LIU, M. P. WALSH, L. SHI, S. NANCE, Y. L. LIU, Y. Y. WANG, G. C. SONG, T. LAMPRECHT, J. EASTON, H. L. MULDER, D. YERGEAU, J. MYERS, J. L. KAMENS, E. A. OBENG, M. PIGAZZI, Marie JAROŠOVÁ, C. KELAIDI, S. POLYCHRONOPOULOU, J. K. LAMBA, S. D. BAKER, J. E. RUBNITZ, D. REINHARDT, M. M. VAN DEN HEUVEL-EIBRINK, F. LOCATELLI, H. HASLE, J. M. KLCO, J. R. DOWNING, J. H. ZHANG, S. POUNDS, C. M. ZWAAN and T. A. GRUBER. Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators. BLOOD CANCER DISCOVERY. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2021, vol. 2, No 6, p. 586-599. ISSN 2643-3230. Available from: https://dx.doi.org/10.1158/2643-3230.BCD-21-0049.

@article{1824557,
   author = {Fornerod, M. and Ma, J. and Noort, S. and Liu, Y. and Walsh, M. P. and Shi, L. and Nance, S. and Liu, Y. L. and Wang, Y. Y. and Song, G. C. and Lamprecht, T. and Easton, J. and Mulder, H. L. and Yergeau, D. and Myers, J. and Kamens, J. L. and Obeng, E. A. and Pigazzi, M. and Jarošová, Marie and Kelaidi, C. and Polychronopoulou, S. and Lamba, J. K. and Baker, S. D. and Rubnitz, J. E. and Reinhardt, D. and Van den HeuvelandEibrink, M. M. and Locatelli, F. and Hasle, H. and Klco, J. M. and Downing, J. R. and Zhang, J. H. and Pounds, S. and Zwaan, C. M. and Gruber, T. A.},
   article_location = {PHILADELPHIA},
   article_number = {6},
   doi = {http://dx.doi.org/10.1158/2643-3230.BCD-21-0049},
   keywords = {Pediatric Myeloid-Related Acute Leukemias; Prognostic Indicators; Integrative Genomic Analysis},
   language = {eng},
   issn = {2643-3230},
   journal = {BLOOD CANCER DISCOVERY},
   title = {Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators},
   url = {https://bloodcancerdiscov.aacrjournals.org/content/2/6/586},
   volume = {2},
   year = {2021}
}

TY  - JOUR
ID  - 1824557
AU  - Fornerod, M. - Ma, J. - Noort, S. - Liu, Y. - Walsh, M. P. - Shi, L. - Nance, S. - Liu, Y. L. - Wang, Y. Y. - Song, G. C. - Lamprecht, T. - Easton, J. - Mulder, H. L. - Yergeau, D. - Myers, J. - Kamens, J. L. - Obeng, E. A. - Pigazzi, M. - Jarošová, Marie - Kelaidi, C. - Polychronopoulou, S. - Lamba, J. K. - Baker, S. D. - Rubnitz, J. E. - Reinhardt, D. - Van den Heuvel-Eibrink, M. M. - Locatelli, F. - Hasle, H. - Klco, J. M. - Downing, J. R. - Zhang, J. H. - Pounds, S. - Zwaan, C. M. - Gruber, T. A.
PY  - 2021
TI  - Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators
JF  - BLOOD CANCER DISCOVERY
VL  - 2
IS  - 6
SP  - 586-599
EP  - 586-599
PB  - AMER ASSOC CANCER RESEARCH
SN  - 26433230
KW  - Pediatric Myeloid-Related Acute Leukemias
KW  - Prognostic Indicators
KW  - Integrative Genomic Analysis
UR  - https://bloodcancerdiscov.aacrjournals.org/content/2/6/586
N2  - Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell-like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification. SIGNIFICANCE: Immunophenotype and somatic mutations play a significant role in treatment approach and risk stratification of acute leukemia. We conducted an integrated genomic analysis of pediatric myeloid malignancies and found that a combination of genetic and transcriptional readouts was superior to immunophenotype and genomic mutations in identifying biological subtypes and predicting outcomes.
ER  -

FORNEROD, M., J. MA, S. NOORT, Y. LIU, M. P. WALSH, L. SHI, S. NANCE, Y. L. LIU, Y. Y. WANG, G. C. SONG, T. LAMPRECHT, J. EASTON, H. L. MULDER, D. YERGEAU, J. MYERS, J. L. KAMENS, E. A. OBENG, M. PIGAZZI, Marie JAROŠOVÁ, C. KELAIDI, S. POLYCHRONOPOULOU, J. K. LAMBA, S. D. BAKER, J. E. RUBNITZ, D. REINHARDT, M. M. VAN DEN HEUVEL-EIBRINK, F. LOCATELLI, H. HASLE, J. M. KLCO, J. R. DOWNING, J. H. ZHANG, S. POUNDS, C. M. ZWAAN and T. A. GRUBER. Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators. \textit{BLOOD CANCER DISCOVERY}. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2021, vol.~2, No~6, p.~586-599. ISSN~2643-3230. Available from: https://dx.doi.org/10.1158/2643-3230.BCD-21-0049.

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