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Annals of Clinical & Laboratory Science 37:34-38 (2007)
© 2007 Association of Clinical Scientists

Morphoproteomic Expression of H-ras (p21ras) Correlates with Serum Monoclonal Immunoglobulin Reduction in Multiple Myeloma Patients Following Pamidronate Treatment

Ping L. Zhang1,3, Albert T. Quiery, Jr.2, Thomas M. Blasick3 and Robert E. Brown1
1 Division of Laboratory Medicine, 2 Department of Adult Hematology & Oncology, and 3 Weis Center for Research, Geisinger Medical Center, Danville, Pennsylvania

Address correspondence to: Ping L. Zhang, M.D., Ph.D., Division of Laboratory Medicine, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA; tel 570 271 6333; fax 570 271 6105; e-mail plzhang{at}geisinger.edu.

Bisphosphonates have been used to treat lytic lesions of multiple myeloma because of their inhibitory effects on osteoclasts. However, their effects on myeloma cells, per se, are not known to be correlated with specific markers. The goal of this study was to assess molecular concomitants of myeloma that might serve as markers for predicting the pharmacologic impact of bisphosphonates on malignant plasma cells. We tested the correlation of serum monoclonal immunoglobulin (Ig) level (IgG and IgA classes) with therapies utilizing two aminobisphosphonates, pamidronate (Aredia) and/or zoledronate (Zometa), in 19 patients with multiple myeloma. Myeloma cells from bone marrow biopsies were immunohistochemically stained for H-ras (p21 ras), N-ras, and the {alpha} subunit common to farnesyl and geranylgeranyl transferase (FT{alpha}/GGT {alpha}). Elevated expression level of H-ras in myeloma cells, rather than N-ras or FT{alpha}/GGT{alpha}, was significantly associated with a decrease of serum monoclonal Ig level following pamidronate treatment. The data suggest that pamidronate may have a direct inhibitory effect on the proliferation of myeloma cells, thus causing reduction in serum monoclonal Ig level. H-ras expression in myeloma cells may prove to be valuable in predicting the therapeutic effects of pamidronate.

Keywords: multiple myeloma, bisphosphonates, pamidronate, zoledronate, H-ras, serum monoclonal Ig






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