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HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-ALL

GSE268574 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/08/06 Platform GPL24676
Summary
Infants diagnosed with acute lymphoblastic leukemia (B-ALL) and t(4;11) chromosomal rearrangements represent a subset of patients with poor therapeutic response. t(4;11) B-ALL cells exhibit low levels of HDAC7, which is essential for optimal B lymphocyte differentiation. Here, we show that HDAC7 silencing in this malignancy is mediated by epigenetic mechanisms involving the chromatin remodeler EZH2 and the KMT2A-AFF1 fusion protein. Remarkably, the menin inhibitor MI-538 restores HDAC7 expression, and this effect is enhanced by the addition of the class I HDAC inhibitor chidamide. This treatment drives leukemic pro-B cells towards a more differentiated and less malignant state, thereby impairing aberrant proliferation. In addition to reducing the malignant capacity of leukemic cells in vitro, addition of MI-538 and chidamide to standard chemotherapy shows promise in reducing the engraftment of t(4;11) pro-B-ALL cells in vivo and delaying relapse. Finally, the newly developed therapy increases the ex vivo glucocorticoid sensitivity of t(4;11) pro-B-ALL primary cells.
Published in
HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-cell acute lymphoblastic leukemia
de Barrios O, Ocón-Gabarró I, Gusi-Vives M et al. · Biomarker research 2025 · PMID 40722046 · doi:10.1186/s40364-025-00810-1
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Also filed as BioProject PRJNA1117828 and SRA study SRP510578. Searching any of these in the dataset finder brings you back here.

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