期刊
BLOOD
卷 130, 期 23, 页码 2499-2503出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2017-05-785683
关键词
-
类别
资金
- Austrian Science Fund (FWF) [P27132-B20, F4701-B20, SFB F4707, SFB-F06105]
- Austrian Federal Ministry of Science, Research and Economy
- National Foundation for Research, Technology and Development
- Oesterreichische Nationalbank (OeNB) [P15936]
- Austrian Science Fund (FWF) [P27132] Funding Source: Austrian Science Fund (FWF)
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2butnotwithexpressionof theBCL-2 familymembersmyeloidcell leukemia1(MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据