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Menin Inhibition

Menin-KMT2A Disruption

In NPM1m and KMT2Ar acute leukemias, menin interacts with KMT2A and can drive a specific transcription program, leading to leukemogenesis.1

With a deeper understanding of the mechanisms that contribute to these specific leukemias, menin-KMT2A interactions become an intriguing target to explore.

Microscopic view of a cell with a bright yellow center and blue background, showcasing cellular structure.
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Adapted from: Uckelmann HJ, et al. Presented at ASH Annual Meeting, 2018. 

 

Menin is a scaffold protein, and its binding to KMT2A leads to transcriptional activation of leukemogenic genes such as HOX and MEIS1. When a menin inhibitor is introduced, it fits into the binding pocket of menin and displaces KMT2A. In disrupting the binding interaction, the HOX and MEIS genes are turned off and leukemic cell growth is halted.

View the mechanism of disease below:

 

References:

  1. Li X, Song Y. J Hematol Oncol. 2021;14:56.