title: Bortezomib is an efficient agent in plasma cell leukemias.
abstract: Plasma cell leukemia (PCL) represents the most aggressive form of monoclonal gammopathy for which new treatment approaches are needed. Here we report the effect of Bortezomib on cells from 4 patients with PCL, as well as the in vivo efficacy on a patient with secondary PCL. Bortezomib reduced PCL numbers and was more efficient in cell growth inhibition than dexamethasone or doxorubicin. Treatment with Bortezomib induced procaspase-3 and poly(ADP-ribose) polymerase cleavage and decreased the amount of extracellular signal regulated kinase (Erk1/2) and phospho-Erk1/2. However, Bortezomib did not substantially affect the levels of the Erk1/2 upstream activating kinase (MEK1), p27 or p21. Finally, we had the opportunity to use Bortezomib in a heavily pretreated patient with overt secondary PCL and severe anemia and thrombocytopenia. Following Bortezomib treatment, circulating plasma cells disappeared; what is more striking, the peripheral blood counts returned to normal, becoming transfusion-independent. These data support the inclusion of Bortezomib in the therapeutic armamentarium of PCL.
authors.affiliation: Centro de Investigación del Cáncer and Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Esparís-Ogando
authors.forename: Adrián
authors.initials: A
authors.lastname: Alegre
authors.forename: Beatriz
authors.initials: B
authors.lastname: Aguado
authors.forename: Gema
authors.initials: G
authors.lastname: Mateo
authors.forename: Norma
authors.initials: N
authors.lastname: Gutiérrez
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000740:Anemia / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000188:drug therapy*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011719:Pyrazines / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000188:drug therapy; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D011065:Poly(ADP-ribose) Polymerases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases