FLT3酪氨酸激酶抑制剂在急性髓系白血病治疗中的研究进展

Recent progress of FMS like tyrosine kinase3inhibitors in the treatment of acute myeloid leukemia

酪氨酸激酶受体FLT3的激活突变是已发现的急性髓系白血病最常见的分子遗传学异常之一。一般说来,这种突变的出现与不良预后相关,因此近年来的研究致力于开发针对这一类型白血病的靶向治疗方案。已有文献报道的小分子FLT3酪氨酸激酶抑制剂已经超过20余种,

FMS like tyrosine kinase3（FLT3） mutations are the most frequent somatic alteration found in acute myeloid leukemia,occurring in one third of patients,and are related with an increased relapse rate and reduced overall survival,it is regarded as a poor prognostic factor.This has led to the development of a number of small molecular tyrosine kinase inhibitors（TKI） with activity against FLT3.Many of them are still in preclinical development,but several have entered clinical phase I and II trails in patients with relapsed AML.Clinical trails have so far demonstrated that inhibitors of FLT3do have clinical activity in patients with FLT3mutant AML,although this activity is often transient and correlates with effective in-vivo suppression of the FLT3target.Multicentre studies are ongoing,looking at the combination of FLT3inhibitors with conventional chemotherapy.As newer,more potent agents are now entering advanced clinical trails,opportunities will emerge for real progress against this grim disease.