Li Li-Hong, Wang Jing, Ke Xiao-Yan
Department of Hematology,Peking University Third Hospital, Beijing 100191,China.
Department of Hematology,Peking University Third Hospital, Beijing 100191,China. E-mail: xykbysy@ 163. com.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1909-1912. doi: 10.7534/j.issn.1009-2137.2016.06.055.
Leukemia carring translocation at the 11q23 locus is referred to MLL-rearranged (MLL-r) leukemia, and the occurrence of this genetic lesion is associated with a poor prognosis. The most common translocation chromosomes are chromosomes 4,9 and 10. Recently MLL protein was found to interact with DOT1L (DOT1-like) protein, which can promote leukemogenesis. A new DOT1L inhibitor EPZ-5676 can selectively inhibit proliferation, promote apoptosis and differentiation, which was also found to act synergistically with anti-AML (acute myeloid leukemia) and anti-ALL (acute lymphoblastic leukemia) drugs. EPZ-5676 can also induce sustained regression in a rat xenograft model of MLL-rearranged leukemia. Now the novel drug is in phase I of clinical trail. The results suggest that the EPZ-5676 is promising. In this article, the mechanism of EPZ-5676 and its research progress are reviwed.
携带11q23位点易位的白血病被称为MLL重排（MLL-r）白血病，这种基因损伤的出现与预后不良相关。最常见的易位染色体是4号、9号和10号染色体。最近发现MLL蛋白与DOT1L（类DOT1）蛋白相互作用，后者可促进白血病发生。一种新的DOT1L抑制剂EPZ-5676可选择性抑制增殖、促进凋亡和分化，还发现它与抗急性髓系白血病（AML）和抗急性淋巴细胞白血病（ALL）药物具有协同作用。EPZ-5676在MLL重排白血病的大鼠异种移植模型中也可诱导持续缓解。目前这种新药正处于临床试验I期。结果表明EPZ-5676很有前景。本文对EPZ-5676的作用机制及其研究进展进行了综述。
