FLT3是III型酪氨酸激酶受体(RTK)。细胞外结构域由5个免疫球蛋白(Ig)结构域组成,有助于二聚体和配体结合。胞内区域有一个近膜结构域,在缺乏配体的情况下发挥自抑制受体的作用,以及一个具有激活环和催化裂解的双叶激酶区域(Klug等,2018年)。FLT3信号通路发生在配体诱导的二聚体化和转自磷酸化后,并通过MAP激酶、PI3K和STAT5等途径促进信号通路。FLT3信号促进细胞增殖和分化,并参与造血。FLT3在30%的急性髓系白血病中发生突变。在AML病例中,约25%的FLT3突变发生在14外显子编码的近膜域区域或酪氨酸激酶域(TKD)内串联重复(ITDs),而约7-10%的AML病例包含TKD内FLT3错义突变(Klug et al, 2018;Daver等人,2019)。这些突变都支持受体的非配体激活,并导致构成性激活和信号转导(Zheng et al, 2004;Klug et al, 2018; Kazi and Roonstrand, 2019). In rare cases, the FLT3 locus is also subject to translocations that generate constitutively active fusion proteins (reviewed in Kazi and Roonstrand, 2019). Oncogenic FLT3 activity can be targeted with tyrosine kinase inhibitors, although resistance often arises due to secondary mutations or activation of bypass pathways (reviewed in Staudt et al, 2018; Daver et al, 2019).