文章：

蛋白酶体在AML中的作用

The role of the proteasome in AML

原文发布日期：2016-12-02

DOI: 10.1038/bcj.2016.112

类型: Review

开放获取: 是

英文摘要：

Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML. Pre-clinical studies have demonstrated that proteasome inhibition disrupts proliferative cell signaling pathways, exhibits cytotoxic synergism with other chemotherapeutics and induces autophagy of cancer-related proteins. Meanwhile, clinical trials incorporating bortezomib into combination chemotherapy regimens have reported a range of responses in AML patients, with complete remission rates >80% in some cases. Taken together, this preclinical and clinical evidence suggests that inhibition of the proteasome may be efficacious in this disease. In an effort to focus further investigation into this area, these recent studies and their findings are reviewed here.

摘要翻译： 

急性髓系白血病（AML）是一种致命的血液系统恶性肿瘤。尽管其遗传和分子图谱已得到充分解析，针对该病的靶向治疗却未能显著改善临床结局。过去十年间，蛋白酶体抑制剂已被证明是多种血液恶性肿瘤的有效治疗策略。以硼替佐米和卡非佐米为代表的蛋白酶体抑制剂已成为多发性骨髓瘤和套细胞淋巴瘤的核心治疗药物。基于这些成功经验，近期涌现出大量探讨蛋白酶体在AML中的作用及其抑制效果的文献。临床前研究表明，蛋白酶体抑制能阻断增殖性细胞信号通路，与其他化疗药物产生细胞毒性协同效应，并诱导癌症相关蛋白的自噬降解。同时，将硼替佐米纳入联合化疗方案的临床试验显示，AML患者出现不同程度的治疗反应，部分病例完全缓解率超过80%。这些临床前与临床证据共同表明，蛋白酶体抑制可能对该疾病具有治疗价值。为促进该领域的深入研究，本文将对相关最新研究及其发现进行系统性综述。

原文链接：

The role of the proteasome in AML