Zhang Hong-Hong, Wang Hong-Sheng, Qian Xiao-Wen, Fan Cui-Qing, Li Jun, Miao Hui, Zhu Xiao-Hua, Yu Yi, Meng Jian-Hua, Cao Ping, Le Jun, Jiang Jun-Ye, Jiang Wen-Jing, Wang Ping, Zhai Xiao-Wen
Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China.
Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China.
Ann Transl Med. 2019 Jul;7(14):296. doi: 10.21037/atm.2019.04.80.
Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by molecular aberrations. Recently, genetic profiling has been fully investigated on ALL; however, the interaction between its genetic alterations and clinical features is still unclear. Therefore, we investigated the effects of genetic variants on ALL phenotypes and clinical outcomes.
Targeted exome sequencing technology was used to detect molecular profiling of 140 Chinese pediatric patients with ALL. Correlation of genetic features and clinical outcomes was analyzed.
T-cell ALL (T-ALL) patients had higher initial white blood cell (WBC) count (34.8×10/L), higher incidence of mediastinal mass (26.9%), more relapse (23.1%), and enriched (23.1%), (23.1%) and (11.5%) mutations. Among the 18 recurrently mutated genes, and mutations occurred more in female patients (P=0.041), and mutants were with higher initial WBC counts (≥50×10/L) (P=0.047 and P=0.041), mutants were with higher minimal residual disease (MRD) level both on day 19 and day 46 (day 19 MRD ≥1%, P=0.039; day 46 MRD ≥0.01%, P=0.031) after induction chemotherapy. Multivariate analysis revealed that initial WBC counts (≥50×10/L), , and mutations were independent risk factors for 3-year relapse free survival (RFS) in ALL. Furthermore, mutations, age (<1 year or ≥10 years), and were independently associated with adverse outcome in B-cell ALL (B-ALL).
and mutations are powerful predictors for adverse outcome in pediatric B-ALL and ALL. Genetic profiling can contribute to the improvement of prognostication and management in ALL patients.
急性淋巴细胞白血病（ALL）是最常见的儿童恶性肿瘤，具有分子异常特征。近年来，对ALL进行了全面的基因谱分析；然而，其基因改变与临床特征之间的相互作用仍不清楚。因此，我们研究了基因变异对ALL表型和临床结局的影响。
采用靶向外显子测序技术检测140例中国儿童ALL患者的分子谱。分析基因特征与临床结局的相关性。
T细胞ALL（T-ALL）患者初始白细胞（WBC）计数较高（34.8×10⁹/L），纵隔肿块发生率较高（26.9%），复发率较高（23.1%），且富集了KMT2A（23.1%）、NOTCH1（23.1%）和PHF6（11.5%）突变。在18个反复突变的基因中，KMT2A和NOTCH1突变在女性患者中更常见（P=0.041），NRAS和KRAS突变体的初始WBC计数较高（≥50×10⁹/L）（P=0.047和P=0.041），PHF6突变体在诱导化疗后第19天和第46天的微小残留病（MRD）水平较高（第19天MRD≥1%，P=0.039；第46天MRD≥0.01%，P=0.031）。多变量分析显示，初始WBC计数（≥50×10⁹/L）、NRAS和KRAS突变是ALL患者3年无复发生存（RFS）的独立危险因素。此外，PHF6突变、年龄（<1岁或≥10岁）和KMT2A在B细胞ALL（B-ALL）中与不良结局独立相关。
KMT2A和PHF6突变是儿童B-ALL和ALL不良结局的有力预测指标。基因谱分析有助于改善ALL患者的预后评估和管理。
