December 2023: $$ MEN1 mutations mediate clinical resistance to menin inhibition

Paper: Nature
Author: Dr. Florian Perner
Institution: Medizinische Hochschule Hannover

Project description:

Acute leukemias driven by genetic alteration in the MLL1 or NPM1 genes require the chromatin adapter protein Menin to sustain leukemogenic gene expression and self-renewal. Inhibitors of Menin are currently tested in clinical trials and show promise in patients with leukemia refractory to available therapies. Despite the efficacy of these novel class of drugs, acquired drug resistance limits the duration of clinical responses. Dr. Perner and his team have identified novel mutations in the gene coding for Menin that lead to weaker drug binding and ultimately resistance and disease relapse. The detailed characterization of the structural basis and molecular determinants of drug resistance in many patients now pave the way for improvements in diagnostic testing as well as the development of second-generation inhibitors with alternative target binding modes.


Perner F., Stein E.M., Wenge D.V., Singh S., Kim J., Apazidis A., Rahnamoun H., Anand D., Marinaccio C., Hatton C., Wen Y., Stone R.M., Schaller D., Mowla S., Xiao W.,10, Gamlen H.A., Stonestrom A.J., Persaud S., Ener E., Cutler J.A., Doench J.G., McGeehan G.M., Volkamer A., Chodera J.D., Nowak R.P., Fischer E.S., Levine R.L.,  Armstrong S.A., Cai S.F. MEN1 mutations mediate clinical resistance to Menin inhibition. 2023. Nature.


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Anne Asschenfeldt
Anne Asschenfeldt
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