Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia.
Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia.
复制标题
DOI：
10.18632/oncotarget.11357
复制
发表时间：
2016-10-04
期刊：
影响因子：
--
通讯作者：
Hyde RK
中科院分区：
文献类型：
--
作者：
Richter L;Wang Y;Hyde RK
16号染色体倒位（inv（16））产生CBFβ-SMMHC融合蛋白，几乎在所有伴有嗜酸性粒细胞增多症（M4 Eo）的急性髓性白血病亚型M4患者中发现。CBFβ-SMMHC的表达是白血病发展的原因，但其活性的分子机制尚不清楚。最近，在确定CBFβ-SMMHC及其结合伴侣，转录因子RUNX 1和组蛋白去乙酰化酶HDAC 8的作用方面取得了重要进展。重要的是，初步试验表明，靶向这些结合伴侣的小分子对CBFβ-SMMHC诱导的白血病有效。本文将讨论CBFβ-SMMHC活性机制的最新研究进展，以及inv（16）AML的新治疗方法。
Inversion of chromosome 16 (inv(16)) generates the CBFβ-SMMHC fusion protein and is found in nearly all patients with acute myeloid leukemia subtype M4 with Eosinophilia (M4Eo). Expression of CBFβ-SMMHC is causative for leukemia development, but the molecular mechanisms underlying its activity are unclear. Recently, there have been important advances in defining the role of CBFβ-SMMHC and its binding partners, the transcription factor RUNX1 and the histone deacetylase HDAC8. Importantly, initial trials demonstrate that small molecules targeting these binding partners are effective against CBFβ-SMMHC induced leukemia. This review will discuss recent advances in defining the mechanism of CBFβ-SMMHC activity, as well as efforts to develop new therapies for inv(16) AML.