伊马替尼耐药后慢性髓细胞白血病患者的治疗研究进展

Research progress in treatment of chronic myeloid leukemia patients with imatinib resistance

慢性髓细胞白血病(CML)是一种发生在多能造血干细胞的恶性骨髓增殖性肿瘤,病程发展缓慢,白细胞增多和脾大是其主要临床特征。酪氨酸激酶抑制剂(TKI)伊马替尼(IM)的引入,改变CML的自然进程,显著提高CML患者的生存率。但是,随着IM应用时间延长,IM耐药已经成为临床治疗CML的主要挑战。目前许多研究正致力于阐明CML的耐药机制和研发新的TKI,迫切需要替代BCR/ABL1融合基因的新药物靶点及新治疗策略,以治疗IM耐药的CML患者。笔者拟就CML患者发生IM耐药后相关TKI和非TKI药物最新研究进展,以及针对CML细胞的特定T细胞反应的免疫学疗法进行综述。

Chronic myeloid leukemia (CML) is a malignant myeloproliferative neoplasm that occurs in pluripotent hematopoietic stem cells. Pathogenesis of CML is slow, and leukocytosis and splenomegaly are main clinical features of patients with CML. The introduction of tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) has changed the natural progression of CML and significantly improved survival of CML patients. However, with the prolonged application of IM, IM resistance has become a major challenge in the treatment of CML. Many studies are currently working to elucidate the mechanisms of CML resistance and to research and develop new TKI. There is a urgent need to replace new drug targets and new therapeutic strategies for BCR/ABL1 fusion gene in response to IM-resistant CML patients. This article focuses on the development of CML-related TKI and non-TKI latest drugs for IM-resistant CML patients, and describes immunological approaches activating specific T cell responses against CML cells.