Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, China.
Clin Lymphoma Myeloma Leuk. 2020 Jun;20(6):e259-e269. doi: 10.1016/j.clml.2019.09.602. Epub 2019 Oct 1.
Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are frequent in acute myeloid leukemia (AML) and have important prognostic and therapeutic implications. FLT3 aberrations have been detected in a smaller fraction of acute lymphoblastic leukemia (ALL), and their prognostic value is not well established. We therefore assessed the FLT3 mutation in Chinese adolescent and adult ALL patients.
We have examined a cohort of 117 Chinese de novo adolescent and adult ALL patients enrolled between June 2016 and June 2017 from the First Affiliated Hospital of Soochow University. Prognostic factors for the ALL patient population were estimated by the Cox regression method. FLT3 mutation was detected by PCR, and its clinical effect was assessed by Kaplan-Meier curves. Differences in FLT3 mutation rate between subgroups were tested by chi-square test.
FLT3 mutations accounted for 6.8% (8/117) in our cohort, including 3 internal tandem duplications (2.6%) and 5 tyrosine kinase domains (4.3%, 3 D835Y mutations, 1 M664I mutation, and 1 I867S mutation), which had no clinical significance on either overall survival (OS) or event-free survival. Alterations in FLT3 occurred more often in early thymic precursor (ETP)-ALL compared to non-ETP T-cell acute lymphoblastic leukemia (P = .028). However, the age at onset (P = .004), initial platelet counts (P = .018), and transplantation status (P = .007) were independent prognostic factors of OS for ALL in multivariate analysis.
The FLT3 mutation was not common in Chinese ALL patients. Age at onset, platelet counts, and transplantation status rather than the presence of the FLT3 mutation were independent prognostic variables for ALL on OS in our cohort. Despite our small sample size, ETP-ALL may indicate a comparable higher FLT3-mutant rate. Because ETP-ALL has been identified as high-risk subgroup, these data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic hematopoietic stem-cell transplantation for FLT3-mutant ETP-ALL.
FMS 样酪氨酸激酶 3（FLT3）的激活突变在急性髓系白血病（AML）中很常见，具有重要的预后和治疗意义。在急性淋巴细胞白血病（ALL）中，FLT3 异常的检出率较低，其预后价值尚未得到充分确立。因此，我们评估了中国青少年和成年 ALL 患者的 FLT3 突变情况。
我们检查了 2016 年 6 月至 2017 年 6 月期间来自苏州大学第一附属医院的 117 例初诊青少年和成年 ALL 患者的队列。使用 Cox 回归方法估计 ALL 患者人群的预后因素。通过 PCR 检测 FLT3 突变，通过 Kaplan-Meier 曲线评估其临床效果。通过卡方检验比较亚组之间 FLT3 突变率的差异。
在我们的队列中，FLT3 突变占 6.8%（8/117），包括 3 个内部串联重复（2.6%）和 5 个酪氨酸激酶结构域（4.3%，3 个 D835Y 突变，1 个 M664I 突变，和 1 个 I867S 突变），这些突变在总生存（OS）或无事件生存方面均无临床意义。与非 ETP-T 细胞急性淋巴细胞白血病相比，FLT3 改变在早期胸腺前体（ETP）-ALL 中更为常见（P =.028）。然而，在多变量分析中，发病年龄（P =.004）、初始血小板计数（P =.018）和移植状态（P =.007）是 ALL 患者 OS 的独立预后因素。
在中国 ALL 患者中，FLT3 突变并不常见。发病年龄、血小板计数和移植状态而非 FLT3 突变是我们队列中 ALL 患者 OS 的独立预后变量。尽管我们的样本量较小，但 ETP-ALL 可能提示更高的 FLT3 突变率。由于 ETP-ALL 已被确定为高危亚组，这些数据需要进行临床研究，除了早期异基因造血干细胞移植外，还应在 FLT3 突变的 ETP-ALL 中实施 FLT3 抑制剂。
