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Epigenetic targets in B- and T-cell lymphomas: latest developments

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THERAPEUTIC ADVANCES IN HEMATOLOGY
卷 14, 期 -, 页码 -

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SAGE PUBLICATIONS LTD
DOI: 10.1177/20406207231173485

关键词

BET inhibitors; bioinformatics; clinical testing; DNMT; drug combination; epigenetics; EZH2; HAT; HDAC; non-Hodgkin's lymphoma

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Non-Hodgkin's lymphomas (NHLs) are a diverse group of diseases characterized by heterogeneous molecular features and clinical manifestations. Epigenetic dysregulations, including mutations in epigenetic enzymes, are prevalent in both B-cell and T-cell lymphomas. Over the past decade, a large number of epigenetic-modifying agents have been developed and introduced in clinical management of NHLs.
Non-Hodgkin's lymphomas (NHLs) comprise a diverse group of diseases, either of mature B-cell or of T-cell derivation, characterized by heterogeneous molecular features and clinical manifestations. While most of the patients are responsive to standard chemotherapy, immunotherapy, radiation and/or stem cell transplantation, relapsed and/or refractory cases still have a dismal outcome. Deep sequencing analysis have pointed out that epigenetic dysregulations, including mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases (DNMTs), are prevalent in both B- cell and T-cell lymphomas. Accordingly, over the past decade, a large number of epigenetic-modifying agents have been developed and introduced into the clinical management of these entities, and a few specific inhibitors have already been approved for clinical use. Here we summarize the main epigenetic alterations described in B- and T-NHL, that further supported the clinical development of a selected set of epidrugs in determined diseases, including inhibitors of DNMTs, histone deacetylases (HDACs), and extra-terminal domain proteins (bromodomain and extra-terminal motif; BETs). Finally, we highlight the most promising future directions of research in this area, explaining how bioinformatics approaches can help to identify new epigenetic targets in B- and T-cell lymphoid neoplasms.

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