TY - JOUR
T1 - Genomic architecture and treatment outcome in pediatric acute myeloid leukemia
T2 - A Children's Oncology Group report
AU - Vujkovic, Marijana
AU - Attiyeh, Edward F.
AU - Ries, Rhonda E.
AU - Goodman, Elizabeth K.
AU - Ding, Yang
AU - Kavcic, Marko
AU - Alonzo, Todd A.
AU - Wang, Yi Cheng
AU - Gerbing, Robert B.
AU - Sung, Lillian
AU - Hirsch, Betsy
AU - Raimondi, Susana
AU - Gamis, Alan S.
AU - Meshinchi, Soheil
AU - Aplenc, Richard
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/6/8
Y1 - 2017/6/8
N2 - 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).
AB - 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).
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U2 - 10.1182/blood-2017-03-772384
DO - 10.1182/blood-2017-03-772384
M3 - Article
C2 - 28411282
AN - SCOPUS:85020517991
SN - 0006-4971
VL - 129
SP - 3051
EP - 3058
JO - Blood
JF - Blood
IS - 23
ER -
