急性髓细胞白血病患者对维奈克拉耐药机制及其治疗策略的研究现状
Current research status on mechanisms and treatment strategies of venetoclax resistance in patients with acute myeloid leukemia
摘要维奈克拉(venetoclax)是一种新型口服选择性小分子B细胞淋巴瘤/白血病因子(BCL)-2抑制剂。癌基因 BCL-2具有抑制细胞凋亡的作用,其广泛表达于包括急性髓细胞白血病(AML)在内的多种血液系统肿瘤细胞,这为维奈克拉内源性诱导AML细胞凋亡提供理论基础。中国AML发病率较高,并且治愈率较低。年龄≤60岁AML患者的治愈率为35%~40%,>60岁者仅为5%~15%。目前,国内外正尝试采用维奈克拉单药或联合用药治疗复发/难治或不适宜接受高强度化疗的AML患者,以期提高这部分患者的生存率。但是部分AML患者对维奈克拉产生原发性或诱导性耐药,导致维奈克拉治疗无效。笔者拟就维奈克拉治疗AML的作用机制,AML患者对维奈克拉的耐药机制及解决维奈克拉耐药治疗策略的研究现状进行阐述,旨在为解决AML患者的维奈克拉耐药问题提供参考。
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abstractsVenetoclax is a novel oral small molecule selective inhibitor of B cell lymphoma/leukemia (BCL-2). Oncogene BCL-2 can inhibit apoptosis and is widely expressed in a variety of hematological tumor cells including acute myeloid leukemia (AML), which provides theoretical basis for endogenous induction of AML cell apoptosis by venetoclax. The incidence of AML is high in China. The cure rate of AML patients under 60 years old is 35%-40%, while that of patients over 60 years old is only 5%-15%. At present, domestic and foreign experts are trying to use venetoclax monotherapy or combination therapy to treat patients with relapsed/refractory AML or patients who are not suitable for intensive chemotherapy, in order to improve survival rate of these patients. However, some AML patients developed primary or induced drug resistance to venetoclax, resulting in failure of venetoclax treatment. This paper summarizes research status on mechanisms of venetoclax in treatment of AML, and mechanisms of venetoclax resistance in AML patients and its treatment strategies, in order to provide reference for solving problems of venetoclax resistance in AML patients.
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