急性髓系白血病FLT3⁃ITD突变的克隆进化基础及其不同特性对预后影响的研究进展

Progress of clonal evolutionary basis of FLT3⁃ITD⁃mutant acute myeloid leukemia and the effect of its different characteristics on the prognosis

FLT3⁃内部串联重复(ITD)突变在急性髓系白血病(AML)中的发生率为20%~30%,其通常提示不良预后,尽管FLT3抑制剂的应用使该型AML患者疗效取得了较大提高,但耐药、复发情况也日渐突显。ITD突变使FLT3在无配体存在的情况下发生二聚体化并持续自活化,引起非配体依赖性磷酸化,而不同ITD特性,包括等位基因比率、长度、插入位点、野生型突变含量以及共突变基因等因素,都会影响患者预后,这些因素背后深层次的机制对临床预后、药物应用及治疗策略都有重要的指导意义。

The incidence of FLT3⁃internal tandem duplication(ITD)mutation in acute myeloid leukemia(AML)is approximately 20%-30%and FLT3⁃ITD mutation generally indicates a poor prognosis.Although FLT3 inhibitors have greatly improved the efficacy of AML patients with this type of AML,relapse and drug⁃resistance increasingly become prominent.ITD mutations lead to dimerization and continuous self⁃activation of FLT3 in the absence of ligands,and cause non⁃ligand⁃dependent phosphorylation.Different characteristics of ITD,including allele ratio,length,insertion site,wild⁃type mutation content and co⁃mutated genes,could affect the prognosis of patients.The underlying mechanism of these factors has an important guiding significance for clinical prognosis,drug application and treatment strategy.