Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: A Children's Oncology Group report

Marijana Vujkovic, Edward F. Attiyeh, Rhonda E. Ries, Elizabeth K. Goodman, Yang Ding, Marko Kavcic, Todd A. Alonzo, Yi Cheng Wang, Robert B. Gerbing, Lillian Sung, Betsy Hirsch, Susana Raimondi, Alan S. Gamis, Soheil Meshinchi, Richard Aplenc

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs) and determine their associations with treatment outcome. Data from Affymetrix and Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring altered genomic regions were identified, and the presence of CNAs was found to be associated with decreased 3-year overall survival (OS), event-free survival (EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI, 1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI, 1.1-2.6, respectively).

Original languageEnglish (US)
Pages (from-to)3051-3058
Number of pages8
JournalBlood
Volume129
Issue number23
DOIs
StatePublished - Jun 8 2017

Bibliographical note

Publisher Copyright:
© 2017 by The American Society of Hematology.

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