天津医药 ›› 2018, Vol. 46 ›› Issue (11): 1245-1248.doi: 10.11958/20180978

• 综述 • 上一篇    下一篇

Bcl-2抑制剂用于急性髓系白血病靶向治疗的研究进展

李越洋, 田晨△   

  1. 天津医科大学肿瘤医院血液科, 国家肿瘤临床医学研究中心, 天津市肿瘤防治重点实验室 (邮编300060)
  • 收稿日期:2018-06-22 修回日期:2018-08-27 出版日期:2018-11-15 发布日期:2018-11-20
  • 通讯作者: 田晨 E-mail:tcgirl2001@sina.com
  • 作者简介:作者想年底前见刊 08-02 胡
  • 基金资助:
    异常骨髓微环境中基质细胞通过Hedgehog信号通路对急性T淋巴细胞白血病发生发展的作用机制研究

Advances in research of Bcl-2 inhibitors in AML targeting therapy

LI Yue-yang, TIAN Chen△   

  1. Department of Hematoloty, Tianjin Medical University Cancer Institute and Hospital, Key laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China
  • Received:2018-06-22 Revised:2018-08-27 Published:2018-11-15 Online:2018-11-20

摘要: 摘要: 急性髓系白血病 (AML) 是成人最常见的急性白血病, 诱导化疗仍是AML的一线治疗手段。但是, 由于 AML诱导化疗毒性较高, 且有高失败率及高复发率的特点, 在AML患者中应用受限。近年来, 去甲基化药物地西他滨和阿扎胞苷在AML表观遗传学治疗中得到深入研究, 已经动摇了诱导化疗在AML治疗中的地位。随着对AML生物学研究的深入, 发现越来越多的靶点可影响AML的生物学进程。针对这些靶点的靶向药物分为3类: 第一类是突变位点抑制剂, 如FLT3和IDH抑制剂; 第二类是调节代谢或信号通路的抑制剂, 如Bcl-2拮抗剂及表观遗传学药物;第三类是靶向细胞毒性药物。2017年美国血液学年会报道, AML靶向治疗最有前景的药物为调节代谢或信号通路的抑制剂, 其中BCL-2抑制剂Venetoclax在AML的临床试验报告被评为本届会议最佳。本文就BCL-2抑制剂在 AML的治疗进展做一综述。

关键词: 白血病, 髓样, 基因, Bcl-2, Bcl-2抑制剂, Venetoclax, Navitoclax

Abstract: Abstract:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Induction chemotherapy is still a first-line treatment for AML. However, due to the high toxicity of AML-induction chemotherapy and the characteristics of high failure rate and high recurrence rate, chemotherapy is limited in patients with AML. In recent years, the treatment of desitabine and azacytidine has been deeply studied in the epigenetic therapy of AML, which has shaken the status of induction chemotherapy in patients with AML. With the development of AML biology, more and more targets have been found to affect the biological process of AML. The targeting drugs for AML can be classified into three categories. The first type is mutant site inhibitors, such as FLT3 and IDH inhibitors. The second type is inhibitors that regulate metabolism or signaling pathway, such as Bcl-2 antagonists and epigenetic drugs. And the third category is targeted cytotoxic drugs. The most promising drugs for AML-targeted treatment were inhibitors regulating metabolism or signaling pathway reported in the 2017 American Society of Hematology Annual meeting. Clinical trial report of Venetoclax, a Bcl-2 inhibitor, won the best abstract of this meeting. This article reviews the progress of Bcl-2 inhibitors in the treatment of AML.

Key words: leukemia, myeloid, genes, Bcl-2, Bcl-2 , Venetoclax, Navitoclax