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

髓系转录因子C/EBPa在t易位的急性髓系白血病中失活（8;21）。失活的机制尚不清楚。我们假设miR-182在正常骨髓分化中被AML1灭活。我们进一步假设，在易位t（8;21）的AML中，AML1失活，因此miR-182表达，其本身阻断C/EBPalpha蛋白的表达，导致髓细胞分化受阻。具体目的如下：具体目的1:miR-182在AML1-ETO相关AML中的功能表征及其对转录因子C/EBPa的影响。特异性目的2:miR-182在粒细胞生成和C/EBPalpha突变aml中的作用。

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.