Repression of CEBPA by MECOM in 3q26 AML leukemia cells represents a central node for therapeutic intervention. The CEBPA +42-kb enhancer is essential for normal hematopoiesis in regulating granulocytic differentiation but thought to be repressed by MECOM in hematopoietic stem cells. Downregulation of MECOM during normal stem cell differentiation results in CEBPA induction. The 3q26 chromosomal translocation co-opts the MECOM regulatory network and is associated with poor-prognosis AML. Sustained MECOM expression promotes an immature and self-renewing cell state, which can be disrupted simply by releasing the repression of the single CEPBA +42-kb enhancer, thus highlighting a key node for the development of new therapeutic strategies.

Repression of CEBPA by MECOM in 3q26 AML leukemia cells represents a central node for therapeutic intervention. The CEBPA +42-kb enhancer is essential for normal hematopoiesis in regulating granulocytic differentiation but thought to be repressed by MECOM in hematopoietic stem cells. Downregulation of MECOM during normal stem cell differentiation results in CEBPA induction. The 3q26 chromosomal translocation co-opts the MECOM regulatory network and is associated with poor-prognosis AML. Sustained MECOM expression promotes an immature and self-renewing cell state, which can be disrupted simply by releasing the repression of the single CEPBA +42-kb enhancer, thus highlighting a key node for the development of new therapeutic strategies.

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