Regulation of leukemia stem cells in MOZ-TIF2 AML

本研究使用两种不同的检测系统来确定MOZ-TIF2 AML干细胞的特性。首先，我们发现BRPF1/HOX通路对MOZ-TIF的白血病发生至关重要。我们的数据表明，BRPF1识别组蛋白修饰，刺激靶基因上的MOZ定位，上调靶基因HoxA9和Hoxa10的转录，最终促进白血病的发展。其次，我们重点研究了PRC1复合物的组分Ring1A和Ring1B，它们在干细胞的调控中起着重要作用。我们发现环1A/B通过抑制Glis2在MOZ-TIF2白血病的维持中发挥关键作用，Glis2强烈促进白血病干细胞的分化。

This study was performed to determine the characteristics of MOZ-TIF2 AML stem cells using two different assay systems. Firstly, we showed that BRPF1/HOX pathway is critical for the leukemogenesis by MOZ-TIF. Our data indicate that BRPF1 recognizes histone modifications and stimulates MOZ localization on target genes, and upregulates transcription of target genes such as HoxA9 and Hoxa10, which finally promotes development of leukemia. Secondary, we focused on Ring1A and Ring1B, the components of PRC1 complex, which plays an important role in the regulation of stem cells. We found that Ring 1A/B play crucial roles in the maintenance of MOZ-TIF2 leukemia through repression of Glis2, which strongly promotes differentiation of leukemia stem cells.