title: Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.
abstract: In this work, effects of bortezomib on apoptosis, clonal progenitor growth, cytokine production, and NF-κB expression in patients with MDS with cytopenias requiring transfusion support are examined. Bortezomib increased apoptosis in marrow mononuclear cells but had no effects on CFU-GM, BFU-E, or CFU-L content. No consistent effects on NF-κB activation in vivo were noted. To further define the role of bortezomib in AML and MDS, we examined it in combination with several targeted agents and chemotherapeutic agents in vitro. Combinations with arsenic trioxide, sorafenib, and cytarabine demonstrated synergistic in vitro effects in AML cell lines.
authors: Department of Medicine, Hematology/Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA. jane liesveld@urmc.rochester.edu
authors: Jane L
authors: JL
authors: Liesveld
authors: Karen E
authors: KE
authors: Rosell
authors: Jeremy
authors: J
authors: Bechelli
authors: Chaohui
authors: C
authors: Lu
authors: Patti
authors: P
authors: Messina
authors: Deborah
authors: D
authors: Mulford
authors: J J
authors: JJ
authors: Ifthikharuddin
authors: Craig T
authors: CT
authors: Jordan
authors: Gordon L
authors: GL
authors: Phillips Ii
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010087:Oxides / Q000494:pharmacology; D010671:Phenylurea Compounds; D011480:Protease Inhibitors / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D001557:Benzenesulfonates; D001897:Boronic Acids; D016207:Cytokines; D010087:Oxides; D010671:Phenylurea Compounds; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D011725:Pyridines; D003561:Cytarabine; D009536:Niacinamide; D000069286:Bortezomib; D000077157:Sorafenib; D051231:Farnesyltranstransferase; D001374:Azacitidine; D000077237:Arsenic Trioxide