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

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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.