Multiple Myeloma and Chronic Lymphocytic Leukemia: Commonalities and Differences in Biology and Therapy

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are monoclonal tumors of differentiated B-cells arising late in life with a protracted clinical course that frequently terminates with signs of dedifferentiation. The major clinical differences (extramedullary spread in CLL, bone marrow confinement in MM) may relate to distinctive tumor cell phenotypes and cytokine networks, explaining the frequent bone involvement and uncommon thrombocytopenia in advanced MM. Cytogenetically, CLL is characterized by relatively uniform chromosomal abnormalities with a predominance of trisomy 12 without further changes with disease progression, whereas complex and seemingly random numeric and structural chromosomal aberrations predominate in MM. Multilineage expression and the association with acute myelogenous leukemia suggest that MM may result from transformation of a pluripotent progenitor cell, whereas CLL is thought to develop from a transformed committed B-cell precursor compartment. Survival of patients with MM and CLL is shorter in the presence of higher tumor burden, reflected in increasing anemia in both diseases and in high levels of serum beta-2-microglobulin in MM. Both tumors respond to alkylating agents providing disease palliation but no cures. Glucocorticoids are highly effective in MM and control autoimmune disease associated more frequently with CLL. The marked efficacy of fludarabine in CLL and its lack of activity in MM may provide additional clues about the different biology of CLL and MM.