Epigenetic Therapy as a Putative Molecular Target to Modulate B Cell Biology and Behavior in the Context of
Thayse Pinheiro da Costa1, Marcia Cury El-Cheikh1, Katia Carneiro1
1Federal University of Rio de Janeiro, Institute of Biological Sciences, Laboratory of Cell Proliferation and Differentiation, Av. Carlos Chagas Filho 373 Room F2-01: 21941-902, Brazil.
Abstract:
Histone Deacetylase- (HDAC-) dependent epigenetic mechanisms have been widely explored in the last decade in different types of malignancies in preclinical studies. This effort led to the discovery and development of a range of new HDAC inhibitors (iHDAC) with different chemical properties and selective abilities. In fact, hematological malignancies were the first ones to have new iHDACs approved for clinical use, such as Vorinostat and Romidepsin for cutaneous T cell lymphoma and panobinostat for multiple myeloma. Besides these promising already approved iHDACs, we highlight a range of studies focusing on the HDAC-dependent epigenetic control of B cell development, behavior, and/or function. Here, we highlight 21 iHDACs which have been studied in the literature in the context of B cell development and/or dysfunction mostly focused on B cell lymphomagenesis. Regardless, we have identified 55 clinical trials using 6 out of 21 iHDACs to approach their putative roles on B cell malignancies; none of them focuses on peritoneal B cell populations. Since cells belonging to this peculiar body compartment, named B1 cells, may contribute to the development of autoimmune pathologies, such as lupus, a better understanding of the HDAC-dependent epigenetic mechanisms that control its biology and behavior might shed light on iHDAC use to manage these immunological dysfunctions. In this sense, iHDACs might emerge as a promising new approach for translational studies in this field. In this review, we discuss a putative role of iHDACs in the modulation of peritoneal B cell subpopulation's balance as well as their role as therapeutic agents in the context of chronic diseases mediated by peritoneal B cells.
Insights
Histone deacetylase inhibitors (iHDACs) show promise in treating B cell malignancies and autoimmune diseases. Further research into their role in peritoneal B1 cells could lead to new therapeutic strategies for chronic conditions.
Area of Science:
- Epigenetics
- Immunology
- Pharmacology
Background:
- Histone deacetylase (HDAC) inhibitors (iHDACs) are emerging epigenetic drugs.
- Hematological malignancies have seen the approval of several iHDACs.
- HDACs play a role in B cell development and function, particularly in lymphomagenesis.
Purpose of the Study:
- To review the role of 21 iHDACs in B cell development and dysfunction.
- To identify clinical trials investigating iHDACs for B cell malignancies.
- To explore the potential of iHDACs in modulating peritoneal B1 cells for autoimmune diseases.
Main Methods:
- Literature review of preclinical and clinical studies on iHDACs.
- Analysis of HDAC-dependent epigenetic mechanisms in B cell biology.
- Focus on B cell lymphomagenesis and peritoneal B1 cell populations.
Main Results:
- 21 iHDACs have been studied in relation to B cell development and dysfunction.
- 55 clinical trials involve 6 iHDACs for B cell malignancies, none targeting peritoneal B cells.
- Peritoneal B1 cells' role in autoimmune diseases like lupus is highlighted.
Conclusions:
- iHDACs show therapeutic potential beyond B cell malignancies, including autoimmune diseases.
- Understanding HDAC-dependent mechanisms in peritoneal B1 cells is crucial.
- iHDACs may offer a novel therapeutic approach for chronic diseases involving peritoneal B cells.
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