Lyu X D, Guo Z, Li Y W, Hu J Y, Fan R H, Song Y P
Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
Department of Hematology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
Zhonghua Nei Ke Za Zhi. 2020 Aug 1;59(8):629-633. doi: 10.3760/cma.j.cn112138-20190924-00652.
To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL). From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated. Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations (0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) (0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ(2)=10.330, 0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ(2)=7.974, 0.047; EFS: χ(2)=10.860, 0.013). Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.
探讨急性淋巴细胞白血病（ALL）患者克隆异质性的特征及临床意义。2016年1月至2019年6月，河南肿瘤医院血液科纳入170例新诊断的ALL患者，其中男性93例，女性77例，中位年龄17（2 - 80）岁。采用高通量测序技术检测52个ALL相关基因。根据变异等位基因频率（VAF）和流式细胞术结果分析突变的克隆异质性。同时评估突变的预后价值。121例（71.2%，121/170）患者检测到基因突变，其中18例（52.9%，18/34）T细胞急性淋巴细胞白血病患者检测到2个或更多克隆，而只有23例（16.9%，23/136）B细胞急性淋巴细胞白血病患者为多基因突变阳性（P<0.01）。基因突变相关的克隆异质性分析显示，NOTCH1突变患者中2个或更多克隆较为常见（13/19例患者）（P<0.01）。3个或更多克隆的患者无事件生存期（EFS）显著低于其他患者（χ²=10.330，P = 0.016）。儿童ALL患者结果相似，多个克隆预示较低的总生存期（OS）和EFS（OS：χ²=7.974，P = 0.047；EFS：χ²=10.860，P = 0.013）。ALL患者的克隆异质性与淋巴细胞谱系的不同起源及发病年龄密切相关，这可能揭示疾病本质并预测临床结局。
