酪氨酸激酶抑制剂治疗儿童急性非淋巴细胞白血病的研究进展

Research progress of tyrosine kinase inhibitors in the treatment of children with acute nonlymphocytic leukemia

急性非淋巴细胞白血病即急性髓系白血病(AML)是一种高度异质性疾病,信号通路异常可能为其发病机制之一,酪氨酸激酶为常见的驱动因素,其抑制剂为研究较多的治疗AML的靶向药物。儿童急性白血病领域常用的酪氨酸激酶抑制剂为伊马替尼(Gleevec)和达沙替尼(Sprycel),索拉非尼(Nexavar)较少应用。在目前AML治疗研究中,酪氨酸激酶抑制剂主要应用于c-kit及FLT3的基因异常所致疾病,也有文献报道应用于ETV6-PDGFRβ融合基因、ETV6-ABL1融合基因AML。靶向药物专一性强、不良反应少,但目前临床应用范围较窄,未来发展方向将是在基因水平为儿童白血病提供更精细的研究结果,进而期待更多更精细的研究为儿童白血病的靶向药物治疗提供理论依据。

Acute myeloid leukemia(AML) is a highly heterogeneous disease, and kinase signaling pathway abnormalities may be a common driving factor for the pathogenesis, tyrosine kinase is a common driving factor, whose inhibitor is more researched to treat AML. In children with acute leukemia, imatinib(Gleevec) and dasatinib(Sprycel) are commonly used, while sorafenib(Nexavar) is seldom. In the current treatment of AML, the tyrosine kinase inhibitor mainly used in c-kit gene and FLT3 abnormalities caused by the disease, also reported in the literature used in ETV6-PDGFRβ fusion gene, ETV6-ABL1 fusion gene. Targeted drug has strong specificity, fewer adverse reactions, but the range of applications is narrow, so the future direction will be at the genetic level to provide a more sophisticated study of childhood leukemia, thereby providing therapeutic target for the targeted drug therapy.