The Menin story in acute myeloid leukaemia-The road to success.
KMT2A rearrangement
Menin
Menin inhibitors
NPM1 mutation
acute myeloid leukaemia
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
06 May 2024
06 May 2024
Historique:
received:
05
03
2024
accepted:
23
04
2024
medline:
7
5
2024
pubmed:
7
5
2024
entrez:
6
5
2024
Statut:
aheadofprint
Résumé
The treatment of acute myeloid leukaemia (AML) has changed fundamentally in the last decade with many new targeted therapies entering clinics. Some of the most interesting agents under development are Menin inhibitors which interfere with the interaction of Menin with wild-type (wt) KMT2A or a KMT2A-fusion protein and thereby downregulate the leukaemic gene expression (MEIS1, PBX3, HOX) in NPM1 mutant or KMT2A-rearranged leukaemia. Other HOX and MEIS1 expressing leukaemias may also be sensitive to Menin inhibition. Following the encouraging results as monotherapy in refractory and relapsed AML, the combination of Menin inhibitors with chemotherapeutic agents and other targeted drugs is being investigated clinically.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Cancer Consortium (DKTK) partner site Frankfurt/Mainz and German Cancer Research Center (DKFZ)
Informations de copyright
© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221.
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022;140(12):1345–1377.
Yokoyama A, Somervaille TCP, 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.
Borkin D, He S, Miao H, Kempinska K, Pollock J, Chase J, et al. Pharmacologic inhibition of the Menin‐MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015;27(4):589–602.
Kühn MWM, Song E, Feng Z, Sinha A, Chen CW, Deshpande AJ, et al. Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov. 2016;6(10):1166–1181.
Krivtsov AV, Evans K, Gadrey JY, Eschle BK, Hatton C, Uckelmann HJ, et al. A Menin‐MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL‐rearranged leukemia. Cancer Cell. 2019;36(6):660–673.e11.
Uckelmann HJ, Kim SM, Wong EM, Hatton C, Giovinazzo H, Gadrey JY, et al. Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia. Science. 2020;367(6477):586–590.
Klossowski S, Miao H, Kempinska K, Wu T, Purohit T, Kim E, et al. Menin inhibitor MI‐3454 induces remission in MLL1‐rearranged and NPM1‐mutated models of leukemia. J Clin Invest. 2020;130(2):981–997.
Issa GC, Aldoss I, DiPersio J, Culeivan B, Stone R, Arelano M, et al. The Menin inhibitor revumenib in KMT2A‐rearranged or NPM1‐mutant leukaemia. Nature. 2023;615(7954):920–924.
Perner F, Stein EM, Wenige DV, Singh S, Kim J, Apazidis A, et al. MEN1 mutations mediate clinical resistance to Menin inhibition. Nature. 2023;615(7954):913–919.
Shi X, Li M, Tan L, Liu Z, Zhu Y, Jonathan T, et al. Purine metabolism modulates leukemia stem cell maintenance in MLL‐rearranged acute leukemia. Blood. 2023;142(Suppl 1):582.
Thomas X. Small molecule Menin inhibitors: novel therapeutic agents targeting acute myeloid leukemia with KMT2A rearrangement of NPM1 mutation. Oncol Ther. 2024;12(1):57–72.
Dzama MM, Steiner M, Rausch J, Sasca D, Schönfeld J, Kunz K, et al. Synergistic targeting of FLT3 mutations in AML via combined Menin‐MLL and FLT3 inhibition. Blood. 2020;136(21):2442–2456.