威尼斯人
奥佐美星
医学
阿糖胞苷
髓系白血病
肿瘤科
低甲基化剂
米多司他林
白血病
CD33
内科学
药理学
慢性淋巴细胞白血病
干细胞
基因表达
川地34
化学
DNA甲基化
基因
生物
生物化学
遗传学
作者
Veronica Guerra,Courtney D. DiNardo,Marina Konopleva
标识
DOI:10.1016/j.beha.2019.05.008
摘要
The prognosis of adult acute myeloid leukemia (AML) remains poor, with the long-term survival rate less than 50%. However, the current paradigms of treatment are changing through a better understanding of the disease genetics and pathophysiology. Since 2017, eight new drugs have been approved by the U.S. Food and Drug Administration for the treatment of AML, including the FLT3 inhibitors midostaurin and gilteritinib, the IDH inhibitors ivosidenib and enasidenib, the anti-CD33 monoclonal antibody gemtuzumab ozogamicin, liposomal daunorubicin and cytarabine, the hedgehog pathway inhibitor glasdegib and the BCL-2 inhibitor venetoclax. Preclinical data demonstrated the anti-leukemic efficacy of venetoclax in AML and its synergy when combined with hypomethylating agents or chemotherapy agents. Clinical trials have demonstrated the clinical benefit of venetoclax-based therapies in newly diagnosed AML, leading to the recent FDA approval of venetoclax in combination with hypomethylating agents or low-dose cytarabine for older adults with newly diagnosed AML. Herein, we focus on the role of single-agent BCL-2 inhibition in AML and review the clinical studies of venetoclax-based combination regimens and the evolving mechanisms of resistance.
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