用蛋白酶体抑制剂硼替佐米治疗人类慢性淋巴细胞白血病细胞可促进细胞凋亡。

Treatment of human chronic lymphocytic leukemia cells with the proteasome inhibitor bortezomib promotes apoptosis.

作者信息

Kelley Todd W, Alkan Serhan, Srkalovic Gordan, Hsi Eric D

机构信息

Department of Clinical Pathology, L11, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA.

出版信息

Leuk Res. 2004 Aug;28(8):845-50. doi: 10.1016/j.leukres.2003.12.010.

DOI:10.1016/j.leukres.2003.12.010

PMID:15203282

Abstract

New options are needed for the treatment of B-cell chronic lymphocytic leukemia (CLL). Proteasome inhibitors represent a potential therapeutic strategy. One such agent, bortezomib, was recently approved for the treatment of refractory multiple myeloma. In this study, lymphocytes were isolated from the blood of CLL patients, treated in vitro with bortezomib, and evaluated for apoptosis by flow cytometry. Bortezomib promoted apoptosis in CLL cells in a dose- and time-dependent manner. At 18 h incubation time, 10 nM bortezomib induced an average 4.27 fold (+/-2.57) increase in the percentage of apoptotic cells versus untreated controls. These data indicate that bortezomib has in vitro activity in CLL and support further investigations of this promising new drug.

摘要

治疗B细胞慢性淋巴细胞白血病（CLL）需要新的方法。蛋白酶体抑制剂是一种潜在的治疗策略。一种这样的药物硼替佐米，最近被批准用于治疗难治性多发性骨髓瘤。在本研究中，从CLL患者血液中分离淋巴细胞，体外给予硼替佐米处理，然后通过流式细胞术评估细胞凋亡情况。硼替佐米以剂量和时间依赖性方式促进CLL细胞凋亡。在孵育18小时时，10 nM硼替佐米诱导凋亡细胞百分比相对于未处理对照平均增加4.27倍（±2.57）。这些数据表明硼替佐米在CLL中有体外活性，并支持对这种有前景的新药进行进一步研究。