Menin–KMT2A protein–protein interface

The **menin–KMT2A protein–protein interface** refers to the highly specific binding between the scaffold protein menin (encoded by the MEN1 gene) and the N-terminal region of KMT2A (lysine methyltransferase 2A, also known as MLL1). This interaction is essential for the oncogenic function of KMT2A fusion proteins in acute leukemias[1][3][5]. Menin acts as a critical cofactor, enabling KMT2A-driven complexes to activate expression of leukemogenic target genes such as HOXA9 and MEIS1, thereby sustaining the leukemic phenotype. Disrupting this interface impairs the assembly and function of these oncogenic transcriptional complexes, providing a rationale for the development of small-molecule menin–KMT2A inhibitors as targeted cancer therapeutics, especially in KMT2A-rearranged and NPM1-mutant AML[3][5][7][1]. This protein–protein interface is now recognized as a validated **therapeutic target** in oncology, particularly for MLL-rearranged leukemias, with several inhibitors advancing through clinical trials.

Other names

Menin–MLL1 protein–protein interfaceMenin–MLL protein–protein interactionMenin–KMT2A/MLL interface

Inhibition of the menin–KMT2A protein–protein interaction, disrupting oncogenic transcriptional complexes in leukemia Downregulation of aberrant HOX/MEIS1 gene expression and leukemic cell self-renewal Induction of differentiation and inhibition of proliferation in leukemia cells