慢性粒细胞白血病(CML)治疗新进展

Update on Emerging Treatments for Chronic Myeloid Leukemia(CML)

慢性粒细胞白血病(CML)是由BCR-ABL融合基因编码的具有持续酪氨酸激酶活性的BCR-ABL蛋白所驱动的一种骨髓增生性肿瘤,发病率随年龄增长而增加。BCR-ABL基因的表达可促使CML中多种信号转导通路的激活,并介导了细胞增殖和生存。酪氨酸激酶抑制剂(TKIs)伊马替尼的使用是当前CML治疗的主要手段,并在体内外显示出了显著的抗白血病活性。近年来通过对CML中复杂的信号通路网络进行分析和研究发现,一些药物和TKIs的联用可发挥协同治疗作用,然而依旧有相当一部分患者面临耐药或不耐受的情况。因此,除了TKIs和造血干细胞移植(HSCT)外,目前CML的治疗方法还包括针对CML干细胞和特异性信号通路设计的靶向药物,免疫疗法作为靶向病人体内微小残留灶(MRD)的补充治疗也逐渐引起了关注。文章将详述目前临床上CML的治疗方法及一些正在开展的临床研究新方向,并展望免疫疗法在CML治疗中的应用前景,以期为CML的治疗方法发展提供新的参考依据。

Chronic myeloid leukemia（ CML） is a myeloproliferative cancer driven by the BCR-ABL fusion gene which codes for a protein with constitutive tyrosine kinase activity. The incidence of CML increases with the age of patients. The expression of BCR-ABL gene can promote the activation of multiple signal transduction pathways in CML,and mediate cell proliferation and survival. Tyrosine kinase inhibitors（ TKIs）,such as Imatinib,are the main drugs of CML treatment. In recent years,the combination of some drugs and TKIs has played a synergistic effect by analyzing and studying the complex signaling pathway network in CML. However,a considerable number of patients still face resistance or intolerance. Therefore,in addition to TKIs and hematopoietic stem cell transplantation（ HSCT）,the current treatment of CML includes targeted drugs designed for CML stem cells and specific signaling pathways.Immunotherapy,as a complementary therapy for minimal residual disease（ MRD） in CML patients,has gradually attracted attention.In this article,the author will elaborate on the current clinical methods of CML treatment and some new directions for clinical research being carried out. Moreover,the author look forward to the application prospect of immunotherapy in CML treatment,in order to provide a new reference for the development of CML treatment methods.