Targeted modulation of HDAC7 improves the outcome of hematological malignancies

Résumé fourni par la source

HDAC7 plays a crucial role in B cell development maintaining cell identity throughout B lymphocyte differentiation. Therefore, its deregulation is linked to hematological malignancies. Infants diagnosed of pro-B acute lymphoblastic leukemia (pro-B-ALL) with t(4;11) chromosomal rearrangement represent a subgroup of patients with poor response to standard therapies and an adverse outcome. Since high levels of HDAC7 entail a significant improvement of their survival, we aimed to establish a precision therapy to restore HDAC7 expression. The administration of this therapy to has demonstrated to reduce leukemogenesis of pro-B-ALL cells in vivo, when applied to patient-derived xenografts. These findings can be translated to other hematological diseases, such as Diffuse Large B Cell Lymphoma (DLBCL), the most common and aggressive type of non-Hodgkin lymphoma. R-CHOP, a combination of chemotherapy and immunotherapy is the standard treatment, but patients with low expression of CD20 are resistant. Remarkably, the induction of HDAC7 in DLBCL cell lines promotes CD20 expression and improves response to R-CHOP treatment, both in vitro and in vivo. Publication History Article published online: 10 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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