A novel combinatorial therapy improves the outcome of t(4;11) infant pro-B-ALL through the precise induction of HDAC7 biomarker

Résumé fourni par la source

Infants younger than one year diagnosed of pro-B acute lymphoblastic leukemia (pro-B-ALL) and t(4;11) chromosomal rearrangement represent a subgroup of patients with adverse outcome, mainly due to their poor response to standard therapy. Our research has shown that expression of B-cell factor HDAC7 doubles their survival. Therefore, unveiling the mechanisms responsible for HDAC7 underexpression is essential to develop novel therapeutic strategies to improve their outcome. In this sense, we have identified a promising combinatorial therapy that precisely triggers HDAC7 in t(4;11) pro-B-ALL. This treatment promotes a whole transcriptomic reprogramming, driving leukemic pro-B cells towards a more differentiated and less malignant B-cell state and altering pathways such as cell proliferation and chromatin remodelling. After in vitro validation, we have obtained promising results in vivo , demonstrating that it reduces leukemogenesis of primary infant t(4;11) pro-B-ALL cells in mice models. Since infants are normally excluded from clinical trials due to short age and vulnerability, this HDAC7-inducing therapy opens a new field in research for personalized treatments in infant leukemia. Publication History Article published online: 12 May 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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