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Cofactor menin is necessary for KMT2A to bind HOX gene promoters. In detail, KMT2A binding menin acts as a transcriptional upregulator of HOX genes and their cofactor MEIS1 (A). Disruption of this chromatin complex (by binding of the menin inhibitors and menin protein) leads to inhibition of the leukemogenic transcription program (downregulation of HOX genes) without affecting normal hematopoiesis (B).
