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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 and Richard Aplenc

Key points

  • Pediatric patients with de novo AML on average acquire 1.14 somatic copy number alterations in a study sample of 446 patients.

  • The presence of copy number alterations is significantly associated with survival in standard-risk patients.

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.

  • Submitted March 14, 2017.
  • Accepted April 4, 2017.