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

TitleGenomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report.
Publication TypeJournal Article
Year of Publication2017
AuthorsVujkovic M, Attiyeh EF, Ries RE, Goodman EK, Ding Y, Kavcic M, Alonzo TA, Wang Y-C, Gerbing RB, Sung L, Hirsch B, Raimondi S, Gamis AS, Meshinchi S, Aplenc R
JournalBlood
Volume129
Start Page3051
Issue23
Pagination3051-8
Date Published2017 Jun
ISSN1528-0020
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 on Children's Oncology Group (COG) studies, AAML0531 (NCT01407757), AAML03P1 (NCT00070174), and CCG2961 (NCT00003790). 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 I (HR 1.7, 95%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). Further studies are required to test the prognostic significant of CNA presence in disease relapse in AML patients.

DOI10.1182/blood-2017-03-772384
Alternate JournalBlood
PubMed ID28411282