The mutational spectrum of FLT3 gene in acute lymphoblastic leukemia is different from acute myeloid leukemia.,Cancer Gene Therapy

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The mutational spectrum of FLT3 gene in acute lymphoblastic leukemia is different from acute myeloid leukemia.
Cancer Gene Therapy ( IF 4.8 ) Pub Date : 2019-07-09 , DOI: 10.1038/s41417-019-0120-z
Yu Zhang ₁ , Yang Zhang ₁ , Fang Wang ₁ , Mingyu Wang ₁ , Hong Liu ₁ , Xue Chen ₁ , Panxiang Cao ₁ , Xiaoli Ma ₁ , Wen Teng ₁ , Xian Zhang ₂ , Hongxing Liu _{1,

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Affiliation

Mutations in FMS-like tyrosine kinase 3 (FLT3) gene occur frequently in acute myeloid leukemia (AML) and are rare in acute lymphoblastic leukemia (ALL). We aimed to analyze the incidence and characteristics of FLT3 mutations in ALL. Amplicon-targeted next-generation sequencing of 58 genes was performed on 1571 patients (AML, n = 829; ALL, n = 742). FLT3 mutations were identified in 5.12% (38/742) of ALL patients. Four types of FLT3 mutations were disclosed, including internal tandem duplication (ITD), tyrosine kinase domain (TKD), juxtamembrane insertion and deletion (JM-INDEL), and juxtamembrane point mutation (JM-PM), which were respectively identified in 1.21, 1.89, 0.67, and 1.89% of patients. The incidence of FLT3-JM-PM (1.89 vs 0.48%, P = 0.009) and the proportion of TKD non-D835 mutations that accounted for the total TKD mutations (57.14 vs 18.18%, P = 0.013) were significantly higher in ALL when compared with AML. FLT3-JM-INDEL were mainly found in B-ALL. In addition, FLT3-JM-INDEL and FLT3-JM-PM were first reported in patients with B-ALL. Patients with FLT3 mutations besides of ITD and/or TKD had a potential response to tyrosine kinase inhibitors. We showed that the mutation spectrum of FLT3 gene in ALL is distinct from AML that will facilitated an in-depth understand of the pathogenesis and provide a guidance for treatment.

中文翻译：

FLT3基因在急性淋巴细胞白血病中的突变谱不同于急性髓细胞白血病。

FMS 样酪氨酸激酶 3 (FLT3) 基因突变在急性髓性白血病 (AML) 中经常发生，在急性淋巴细胞白血病 (ALL) 中很少见。我们旨在分析 ALL 中 FLT3 突变的发生率和特征。对 1571 名患者（AML，n = 829；ALL，n = 742）进行了 58 个基因的扩增子靶向下一代测序。在 5.12% (38/742) 的 ALL 患者中发现了 FLT3 突变。公开了四种类型的FLT3突变，包括内部串联重复（ITD）、酪氨酸激酶结构域（TKD）、近膜插入和缺失（JM-INDEL）和近膜点突变（JM-PM），分别在1.21中确定， 1.89、0.67 和 1.89% 的患者。FLT3-JM-PM 的发生率（1.89 对 0.48%，P = 0.009）和 TKD 非 D835 突变占总 TKD 突变的比例（57. 与 AML 相比，ALL 的 14% vs 18.18%，P = 0.013）显着更高。FLT3-JM-INDEL主要存在于B-ALL中。此外，在 B-ALL 患者中首次报道了 FLT3-JM-INDEL 和 FLT3-JM-PM。除了 ITD 和/或 TKD 外，还有 FLT3 突变的患者对酪氨酸激酶抑制剂有潜在的反应。我们发现ALL中FLT3基因的突变谱不同于AML，这将有助于深入了解发病机制并为治疗提供指导。

更新日期：2019-11-18

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