 |
Related Articles |
LBH589 enhances T-cell activation in vivo and accelerates graft-versus-host disease in mice.
Biol Blood Marrow Transplant. 2012 Jun 11;
Authors: Wang D, Iclozan C, Liu C, Xia C, Anasetti C, Yu XZ
Abstract
Histone deacetylase inhibitors (HDACi) are a new class of compounds that induce acetylation of histone lysine tails in chromatin and modify gene expression. The FDA approved HDACi, Vorinostat or suberoylanilide hydroxamic acid (SAHA), has been shown to inhibit tumor cell growth and the production of pro-inflammatory cytokines. In preclinical allogeneic transplantation models, SAHA induces graft-versus-host disease (GVHD) amelioration in treated mice without impairing graft-versus-leukemia (GVL). LBH589 (Panobinostat), a structurally novel cinnamic hydroxamic acid class, is an HDACi more potent than SAHA. In the current work, we tested the hypothesis that LBH589 would be highly effective in the prevention of GVHD. Using mouse model of allogeneic bone marrow transplantation (BMT), we unexpectedly found that treatment with LBH589 accelerated GVHD, in contrast to the treatment with SAHA that alleviated GVHD. Accelerated GVHD in the recipients treated with LBH589 was associated with elevated Th1 cytokines in recipient serum, enhanced CXCR3 expression on donor T cells, and T-cell infiltration in the liver. The current study highlights the distinct effects of pan HDACi on allogeneic BMT, and alerts that LBH589 (Panobinostat) could have adverse effect on GVHD, and possibly on other inflammatory diseases.
PMID: 22698484 [PubMed - as supplied by publisher]
Source: http://www.ncbi.nlm.nih.gov/PubMed/22698484?dopt=Abstract