title: Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
abstract: Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting.
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA; Michigan State University College of Human Medicine, Grand Rapids, MI, USA. Electronic address: A.Samer.Al-Homsi@SpectrumHealth.org.
authors.forename: Ahmad Samer
authors.initials: AS
authors.lastname: Al-Homsi
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA; Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Duffner
authors.affiliation: Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope, Duarte, CA, USA.
authors.forename: Monzr M
authors.initials: MM
authors.lastname: Al Malki
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Goodyke
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Cole
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Marlee
authors.initials: M
authors.lastname: Muilenburg
authors.affiliation: Blood and Marrow Transplantation Program, Spectrum Health, Grand Rapids, MI, USA; Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
authors.forename: Aly
authors.initials: A
authors.lastname: Abdel-Mageed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069286:Bortezomib / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D000069286:Bortezomib