Abdelfattah Nesma E, Elsayed Ghada M, Soliman Amira H, Ebeid Emad N, El Ashry Mona S
Clinical Pathology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, 4 Form El Khalig, Cairo, 11796, Egypt.
Pediatric Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Ann Hematol. 2025 Mar;104(3):1821-1832. doi: 10.1007/s00277-024-06102-2. Epub 2024 Nov 26.
Genetic abnormalities provide diagnostic and prognostic information for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. The aim of this study was to determine the effects of genetic CNAs and RUNX1 gene abnormalities on the outcome of pediatric BCP-ALL patients. This study included 78 de novo-BCP-ALL pediatric patients who presented to the Pediatric Oncology Department of the National Cancer Institute (NCI), Cairo University. We aimed to study the impact of copy number alteration (CNA) of 8 of the most altered genes in BCP-ALL patients, in addition to RUNX1 gene abnormalities, on patient survival and response to treatment. Multiplex ligation-dependent probe amplification (MLPA) was used to detect CNA, while RUNX1 gene alterations were detected by fluorescence in situ hybridization (FISH). CNA of the PAX5 gene was significantly associated with worse overall survival (OS) and event-free survival (EFS) (P = 0.012 and P = 0.025, respectively). An increase in the CNA of ETV6 was associated with an increase in minimal residual disease (MRD) on day 15 (P = 0.041). Although RUNX1 gene abnormalities were not a predictor of shorter OS or EFS, an interesting significant association was found between PAX5 CNA and RUNX1 gene gain and translocation (P = 0.017 and P = 0.041, respectively). PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.
基因异常可为儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）患者提供诊断和预后信息。本研究的目的是确定基因拷贝数变异（CNA）和RUNX1基因异常对儿童BCP-ALL患者预后的影响。本研究纳入了78例初发BCP-ALL儿童患者，这些患者均就诊于开罗大学国家癌症研究所（NCI）的儿科肿瘤科。我们旨在研究BCP-ALL患者中8个最常发生改变的基因的拷贝数改变（CNA）以及RUNX1基因异常对患者生存和治疗反应的影响。采用多重连接依赖探针扩增技术（MLPA）检测CNA，同时通过荧光原位杂交（FISH）检测RUNX1基因改变。PAX5基因的CNA与较差的总生存期（OS）和无事件生存期（EFS）显著相关（分别为P = 0.012和P = 0.025）。ETV6基因CNA的增加与第15天的微小残留病（MRD）增加相关（P = 0.041）。虽然RUNX1基因异常不是较短OS或EFS的预测指标，但在PAX5 CNA与RUNX1基因获得及易位之间发现了有趣的显著关联（分别为P = 0.017和P = 0.041）。PAX5 CNA是一个不良预后因素。ETV6 CNA与第15天的高MRD相关。
