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Editorial
. 2024 Sep 12;144(11):1139-1140.
doi: 10.1182/blood.2024025760.

A menin-KMT2A inhibitor to overcome resistance

Caroline A Heckman  1
Affiliations
Editorial

A menin-KMT2A inhibitor to overcome resistance

Caroline A Heckman. Blood. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: C.A.H. declares no competing financial interests.

Figures

None
JNJ-75276617 (bleximenib) is active in the presence of wild-type and mutated menin. Mutations to MEN1 (menin), such as M327I and T349M, have been observed in patients with acquired clinical resistance to the menin-KMT2A inhibitor revumenib. Kwon et al show that the menin-KMT2A inhibitor JNJ-75276617 can block the interaction between KMT2A and wild-type menin or menin bearing the M327I or T349 mutation. JNJ-75276617 is also effective at inhibiting proliferation of cells expressing wild-type or mutant menin.
See this image and copyright information in PMC

Comment on

  • Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.
    Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, Marien A, Goffin D, Wenge DV, Yue H, Cutler JA, Jin C, Perner F, Hogeling SM, Shaffer PL, Jacobs F, Vinken P, Cai W, Keersmaekers V, Eyassu F, Bhogal B, Verstraeten K, El Ashkar S, Perry JA, Jayaguru P, Barreyro L, Kuchnio A, Darville N, Krosky D, Urbanietz G, Verbist B, Edwards JP, Cowley GS, Kirkpatrick R, Steele R, Ferrante L, Guttke C, Daskalakis N, Pietsch EC, Wilson DM, Attar R, Elsayed Y, Fischer ES, Schuringa JJ, Armstrong SA, Packman K, Philippar U. Kwon MC, et al. Blood. 2024 Sep 12;144(11):1206-1220. doi: 10.1182/blood.2023022480. Blood. 2024. PMID: 38905635 Free PMC article.

References

    1. Kwon MC, Thuring JW, Querolle O, et al. Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. Blood. 2024;144(11):1206–1220. - PubMed
    1. Yokoyama A, Somervaille TC, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell. 2005;123(2):207–218. - PubMed
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    1. Issa GC, Aldoss I, DiPersio J, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023;615(7954):920–924. - PMC - PubMed

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