C/EBPalpha-repressed microRNA-182 in stem cell differentiation and leukemia

C/EBPα 抑制干细胞分化和白血病中的 microRNA-182

• 批准号: 239711321
• 负责人: Professor Dr. Gerhard Behre
• 金额: --
• 依托单位: Klinik für Innere Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/239711321?language=en
• 关键词: EBPalpha; repressed; microRNA; 182; stem

Myeloid transcription factor C/EBPa is inactivated in acute myeloid leukemia with translocation t(8;21). The mechanism of the inactivation is poorly unterstood. We hypothesize that miR-182 is inactivated by AML1 in normal myeloid differentation. We further hypothesize that in AML with translocation t(8;21) AML1 is inactivated, thereby miR-182 is expressed and itself blocks C/EBPalpha protein expression leading to a block in myeloid differentiation. The specific aims are the following: specific aim 1: functional characterization of miR-182 in AML1-ETO associated AML and its effect on transcription factor C/EBPa. Specific aim 2: the role of miR-182 in granulopoiesis and in AMLs with C/EBPalpha mutation.

髓系转录因子C/EBPA在t(8；21)易位的急性髓系白血病中失活。其失活机制尚不清楚。我们假设，在正常的髓系分化中，miR-182被AML1灭活。我们进一步假设，在t(8；21)易位的AML中，AML1失活，从而miR-182表达，并自身阻断C/EBPalpha蛋白的表达，导致髓系分化受阻。具体目标如下：特异性目标1：AML1-ETO相关AML中miR-182的功能特征及其对转录因子C/EBPA的影响。特定目的2：miR-182在粒细胞生成和C/EBPalpha突变的急性髓系白血病中的作用。