Bortezomib is an efficient agent in plasma cell leukemias.
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.
Esparís-Ogando
Azucena
A
Centro de Investigación del Cáncer and Hospital Universitario de Salamanca, Salamanca, Spain.
Alegre
Adrián
A
Aguado
Beatriz
B
Mateo
Gema
G
Gutiérrez
Norma
N
Bladé
Joan
J
Schenkein
David
D
Pandiella
Atanasio
A
San Miguel
Jesús F
JF
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
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