title: Treatment of human chronic lymphocytic leukemia cells with the proteasome inhibitor bortezomib promotes apoptosis.
abstract: New options are needed for the treatment of B-cell chronic lymphocytic leukemia (CLL). Proteasome inhibitors represent a potential therapeutic strategy. One such agent, bortezomib, was recently approved for the treatment of refractory multiple myeloma. In this study, lymphocytes were isolated from the blood of CLL patients, treated in vitro with bortezomib, and evaluated for apoptosis by flow cytometry. Bortezomib promoted apoptosis in CLL cells in a dose- and time-dependent manner. At 18 h incubation time, 10 nM bortezomib induced an average 4.27 fold (+/-2.57) increase in the percentage of apoptotic cells versus untreated controls. These data indicate that bortezomib has in vitro activity in CLL and support further investigations of this promising new drug.
authors.affiliation: Department of Clinical Pathology, L11, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Kelley
authors.forename: Serhan
authors.initials: S
authors.lastname: Alkan
authors.forename: Gordan
authors.initials: G
authors.lastname: Srkalovic
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003546:Cysteine Endopeptidases; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex