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BH3 mimetic therapies for CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia.

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Trends in molecular medicine 2026 Vol.32(4) p. 326-337
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Capdevielle C, St-Amand S, Neault M, Gruber TA, Cellot S, Mallette FA

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Pediatric acute megakaryoblastic leukemia (AMKL) associated with the CBFA2T3::GLIS2 (CG2) gene fusion is distinctive by virtue of its aggressiveness and ability to transform normal cells in a single e

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APA Capdevielle C, St-Amand S, et al. (2026). BH3 mimetic therapies for CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia.. Trends in molecular medicine, 32(4), 326-337. https://doi.org/10.1016/j.molmed.2025.09.006
MLA Capdevielle C, et al.. "BH3 mimetic therapies for CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia.." Trends in molecular medicine, vol. 32, no. 4, 2026, pp. 326-337.
PMID 41058336 ↗

Abstract

Pediatric acute megakaryoblastic leukemia (AMKL) associated with the CBFA2T3::GLIS2 (CG2) gene fusion is distinctive by virtue of its aggressiveness and ability to transform normal cells in a single event. The dismal therapeutic response of children to this disease has stimulated comprehensive studies on the molecular mechanism of CG2-driven tumorigenesis. In this Opinion, we highlight various investigative strategies, used in parallel by multiple independent research teams, that point to a specific dependence of CG2-expressing leukemias on the B cell leukemia/lymphoma-2 (BCL-2) family of antiapoptotic proteins. We propose that this intrinsic feature renders these leukemias particularly vulnerable to BCL-2 homology 3 (BH3) mimetics.

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