(A and B) In normal cells, KDM1A activates or represses genes through its histone demethylase activity (A), maintaining the balance between hematopoietic stem cells and differentiation to mature myeloid cells (B).
(C) In AML, increased KDM1A expression promotes an oncogenic gene expression program, causing a block in differentiation associated with increased H3K4me3 to H3K4me2 ratio at the promoter of target genes. Inhibition of KDM1A restores this balance, promoting blast cell differentiation.