Histone Modifications and Their Targeting in Lymphoid Malignancies

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected gene...

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Detalles Bibliográficos
Autores: Fernández-Serrano, Miranda|||0000-0001-9040-8496, Winkler, René|||0000-0002-7570-0242, Santos, Juliana|||0000-0003-4148-9570, Le Pannérer, Marguerite Marie|||0000-0002-5779-8805, Buschbeck, Marcus|||0000-0002-3218-4567, Roué, Gaël|||0000-0003-0245-2257
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252172
Acceso en línea:https://ddd.uab.cat/record/252172
https://dx.doi.org/urn:doi:10.3390/ijms23010253
Access Level:acceso abierto
Palabra clave:Non-Hodgkin lymphoma
Epigenetics
DNA methylation
HAT
HDAC
EZH2
Bromodomain inhibitors
Drug combination
Clinical testing
Descripción
Sumario:In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients.