title: Proteasome inhibitors in acute leukemia.
abstract: Proteasome inhibition has been recognized as a novel treatment modality in hematologic malignancies. Initially, the reversible proteasome inhibitor bortezomib demonstrated efficacy in multiple myeloma (MM), which supported its approval for relapsed and refractory MM in 2003. Later on, carfilzomib, a next-generation irreversible proteasome inhibitor was approved by the US FDA in July 2012 for relapsed/refractory MM. Currently, several other proteasome inhibitors are undergoing preclinical and clinical evaluation. The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia. The first clinical studies with bortezomib in leukemia revealed promising clinical activity, particularly when combined with conventional chemotherapeutics. In this review the position of proteasome inhibitors in acute leukemia treatment is summarized and discussed. Special focus is also attributed to immunoproteasome inhibitors. As a future perspective, it is anticipated that proteasome inhibitors may prove to be of added value in therapeutic interventions for acute leukemia.
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Denise
authors.initials: D
authors.lastname: Niewerth
authors.forename: Ilse
authors.initials: I
authors.lastname: Dingjan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cloos
authors.forename: Gerrit
authors.initials: G
authors.lastname: Jansen
authors.forename: Gertjan
authors.initials: G
authors.lastname: Kaspers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology; D061988:Proteasome Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors