Therapeutic bortezomib administration protects mice from sclerodermatous cGVHD responses. Irradiated (800 cGy) recipient BALB/c mice received bone marrow cells (8 million) with or without spleen cells (25 million) intravenously from donor B10.D2 mice. Mice were then randomized allocated to treat with either vehicle (PBS) or bortezomib (0.1 mg/kg) intraperitoneally at day 20 after transplant and every 5 days thereafter. (A) Skin clinical scores (on a scale of 3.9) were evaluated twice a week. (B) Photographs were taken at day 55 after HSCT from either bone marrow only or GVHD mice treated with vehicle or bortezomib at day 20. (C) (Upper) Pathologic examination of skin by hematoxylin and eosin stain. (Lower) Collagen deposition and fibrosis were examined by Masson’s trichrome stain. (D) Pathological scores (on a scale of 10) were evaluated by pathologists in a blind code fashion. Data are shown as mean ± standard error of the mean (SEM) and analyzed by 1- or 2-way ANOVA with a Tukey post hoc test to compare between individual groups. *P < .05, **P < .01, and ***P < .001 were considered significant. Data were collected from 2 independent experiments with 8 mice per group.