BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice.

Blood
Yaping SunPavan Reddy

Abstract

Acute graft-versus-host disease (GVHD) is the major obstacle of allogeneic bone marrow transplantation (BMT). Bromodomain and extra-terminal (BET) protein inhibitors selectively block acetyl-binding pockets of the bromodomains and modulate histone acetylation. Here, we report that inhibition of BET bromodomain (BRD) proteins with I-BET151 alters cytokine expression in dendritic cells (DCs) and T cells, including surface costimulatory molecules, in vitro and in vivo cytokine secretion, and expansion. Mechanistic studies with I-BET151 and JQ1, another inhibitor, demonstrate that these effects could be from disruption of association between BRD4 and acetyl-310 RelA of nuclear factor kappa B. Short-term administration early during BMT reduced GVHD severity and improved mortality in two different allogeneic BMT models but retained sufficient graft-versus-tumor effect. Thus inhibiting BRD proteins may serve as a novel approach for preventing GVHD.

References

May 1, 1997·Trends in Biochemical Sciences·F JeanmouginR Losson
Mar 26, 2002·FEBS Letters·Lei Zeng, Ming Ming Zhou
Mar 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Pavan ReddyJames L M Ferrara
Dec 24, 2008·Molecular and Cellular Biology·Bo HuangLin-Feng Chen
Mar 14, 2009·Lancet·James L M FerraraErnst Holler
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yaping SunPavan Reddy
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Nov 12, 2010·Nature·Edwige NicodemeAlexander Tarakhovsky
Sep 6, 2011·Cell·Jake E DelmoreConstantine S Mitsiades
Mar 23, 2012·Bioorganic & Medicinal Chemistry Letters·Jonathan SealRab K Prinjha
May 12, 2012·Nature Reviews. Immunology·Bruce R BlazarMehrdad Abedi
Aug 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hozefa S BandukwalaAnjana Rao
Feb 20, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna C BelkinaGerald V Denis
Oct 9, 2013·The Journal of Experimental Medicine·Deanna A MeleJose M Lora

❮ Previous
Next ❯

Citations

Nov 18, 2015·Journal of Medicinal Chemistry·Frank Anthony RomeroSteven Magnuson
Nov 22, 2015·International Immunopharmacology·Shitong WeiHongyu Sha
Mar 13, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Armin RashidiDaniel J Weisdorf
Oct 23, 2016·Drug Discovery Today. Technologies·Srimoyee Ghosh, Jose M Lora
Jan 13, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Suzanne AcklooSusanne Müller
Feb 9, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·B Suarez-AlvarezC Lopez-Larrea
Apr 24, 2020·Circulation Research·Patricia Cristine BorckJorge Plutzky
Oct 30, 2016·Oncotarget·Michela BoiUNKNOWN AIRC 5xMille Consortium ‘Genetics-Driven Targeted Management of Lymphoid Malignancies’
Mar 29, 2016·British Journal of Haematology·John MagenauPavan Reddy
Jul 12, 2020·Cancer Immunology, Immunotherapy : CII·Niklas RemkePeter Brossart
Feb 12, 2020·International Immunopharmacology·Urban Švajger, Primož J Rožman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.