Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1.

doi:10.3324/haematol.2024.286833

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Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1.

Haematologica - 1 May 2026

Ciaurro Valerio, Sharlandjieva Vassilena, Skwarska Anna, Chahrour Catherine, Baran Natalia, Zeng Zhihong, Ramage Cassandra, Daver Naval, Carter Bing Z, Chaundhry Sovira, Thandapani Palaniraja, Martelli Maria Paola, Milne Thomas A, Konopleva Marina

Abstract excerpt

Mixed-lineage leukemia (MLL) rearrangements (MLLr) and nucleophosmin-1 (NPM1) mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL. We hypothesized that targeting the menin-MLL interaction using DS-1594b and blocking the anti-apoptotic BCL-2 protein using venetoclax may promote differentiation and enhance eradication of...

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PMID: 41195508
DOI: 10.3324/haematol.2024.286833
PMCID: PMC13136833

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NPM1

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