酪氨酸激酶抑制剂在儿童Ph阳性急性淋巴细胞白血病的治疗进展

急性淋巴细胞白血病(ALL)是儿童最常见的血液系统恶性疾病,其中有3％～5％患儿存在Ph染色体,即断裂点簇集区/Abelson白血病病毒(BCR/ABL)1融合基因,其分子发病机制是t(9;22)(q34;q11)染色体易位,使得酪氨酸激酶持续活化,细胞无限增殖.携带该融合基因的ALL患儿预后差,复发率高.近年,针对该融合基因的分子靶向药物,酪氨酸激酶抑制剂(TKI)的使用改善了Ph+ ALL治疗效果,完全缓解(CR)率和生存率都得到了大幅提高,一定程度上代替了异基因造血干细胞移植(allo-HSCT).另外,相关研究也探讨了TKI的副作用与耐药机制等安全性和长期有效性问题.笔者拟就TKI治疗儿童Ph+ ALL的临床疗效、不良反应、耐药机制等方面的研究进展进行综述,旨在为TKI的临床广泛应用提供理论基础.

Progress of tyrosine kinase inhibitors in treating Ph positive acute lymphoblastic leukemia in children

Acute lymphoblastic leukemia (ALL)is the most common cancer in children and the presence of Philadelphia chromosome or breakpoint cluster region/Abelson leukemia virus (BCR/ABL) 1 fusion gene which accounting for 3 ％-5 ％ in ALL is an adverse prognostic factor associated with a high risk of therapeutic failure and relapse.It's pathogenic mechanism is activating the tyrosine kinase and cell proliferate persistently.Recently,tyrosine kinase inhibitors(TKI) have improved the complete remission (CR) and survival rate greatly,and somehow replace the allogeneic hematopoietic stem cell transplantation (allo-HSCT).In addition,some researches still concern the adverse effects and resistence to TKI.Here,we review the progress of clinical effciency,adverse effect and resistence mechanisms of TKI and discuss the challenges and future prospects.