Menin-KMT2A complex (protein-protein interaction)

The **menin-KMT2A interaction** refers to the binding between menin, a scaffolding protein encoded by the MEN1 gene, and KMT2A (also known as MLL1, a histone-lysine N-methyltransferase). This interaction is essential for the transcriptional activation of key developmental genes, notably the HOX gene cluster, by maintaining active chromatin states through H3K4 methylation[1][3][6]. In hematopoietic malignancies such as acute myeloid leukemia and acute lymphoblastic leukemia, especially those with KMT2A gene rearrangements or mutations in NPM1, the menin-KMT2A interaction becomes a critical oncogenic driver by sustaining aberrant gene expression programs that block differentiation and promote proliferation of leukemic blasts[3][5][7]. Therapeutically, targeted inhibition of this protein-protein interaction using small molecules (e.g., revumenib, JNJ-75276617) disrupts oncogenic transcription, induces differentiation, and leads to apoptosis of leukemia cells[5][7]. This provides a compelling mechanism-based strategy for treating high-risk leukemias with KMT2A or NPM1 genetic alterations, with numerous agents in clinical development.

Other names

Menin-MLL1 interactionMEN1-KMT2A interactionMenin-MLL fusion protein interactionMenin-histone-lysine N-methyltransferase 2A interaction

Inhibition of menin-KMT2A protein-protein interaction, causing dissociation of the complex from chromatin, downregulation of oncogenic transcription programs (notably HOXA and MEIS1 genes), reversal of differentiation block, and induction of apoptosis in leukemia cells[5][7].