Vujkovic Marijana, Attiyeh Edward F, Ries Rhonda E, Goodman Elizabeth K, Ding Yang, Kavcic Marko, Alonzo Todd A, Wang Yi-Cheng, Gerbing Robert B, Sung Lillian, Hirsch Betsy, Raimondi Susana, Gamis Alan S, Meshinchi Soheil, Aplenc Richard
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Blood. 2017 Jun 8;129(23):3051-3058. doi: 10.1182/blood-2017-03-772384. Epub 2017 Apr 14.
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). Additional studies are required to test the prognostic significance of CNA presence in disease relapse in patients with AML. COG studies AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials.gov as #NCT01407757, #NCT00070174, and #NCT00003790, respectively.
儿童急性髓系白血病（AML）常以染色体不稳定为特征。约50%的患者会出现疾病复发，因此需要新的预后标志物来改善风险分层。我们对参加儿童肿瘤学组（COG）研究AAML0531、AAML03P1和CCG2961的446例初治AML患儿进行了全基因组基因分型。使用Affymetrix和Illumina Omni 2.5平台评估拷贝数改变（CNA），并确定其与治疗结果的关联。来自Affymetrix和Illumina研究的数据使用ASCAT和GISTIC软件进行联合分析。每位患者平均观察到1.14个体细胞获得性CNA。鉴定出了新的反复出现的基因组改变区域，并且发现CNA的存在与诱导治疗1结束后的3年总生存期（OS）、无事件生存期（EFS）降低以及复发风险相关（风险比[HR]分别为1.7；95%置信区间[CI]为1.2 - 2.4；HR为1.4；95% CI为1.0 - 1.8；以及HR为1.4；95% CI为1.0 - 2.0）。按风险组分析显示仅在标准风险组中OS和EFS降低（HR分别为1.9；95% CI为1.1 - 3.3和HR为1.7；95% CI为1.1 - 2.6）。需要进一步研究来检验AML患者疾病复发时CNA存在的预后意义。COG研究AAML0531、AAML03P1和CCG2961分别在www.clinicaltrials.gov上注册为#NCT01407757、#NCT00070174和#NCT00003790。
