04.19.22

BET-Bromodomain and EZH2 Inhibitor Treated Chronic GVHD Mice

Zaiken MC, Flynn R, Paz KG, et al. BET-Bromodomain and EZH2 Inhibitor Treated Chronic GVHD Mice Have Blunted Germinal Centers With Distinct Transcriptomes. Blood. 2022; (doi: 10.1182/blood.2021014557).

Anti-cancer enzyme inhibitors disrupt the germinal center (GC) in mice that is necessary for chronic graft-versus-host disease (cGVHD) to develop after allogeneic hematopoietic stem cell transplant, making them promising therapeutic targets. In a murine model of cGVHD with bronchiolitis obliterans (BO), both the novel Enhancer of Zeste Homolog 2 (EZH2) inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 also improved pulmonary function. While the inhibitors appear to deliver similar physiological outcomes, researchers learned they do so via different transcriptional changes that then independently interfere with GC response. After studying the transcriptomes of splenic GC B cells (GCBs) from transplanted mice treated with JQ1 or JQ5, they determined that each drug reduced multiple inflammatory and signaling pathways enriched in cGVHD/BO GCBs.

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