Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor CCAAT Enhancer Binding protein a

The transcription factor C/EBP is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBP blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBP-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBP-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBP cooperates with other events in the development of leukemia. Therefore, C/EBP is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.