title: Morphoproteomic expression of H-ras (p21ras) correlates with serum monoclonal immunoglobulin reduction in multiple myeloma patients following pamidronate treatment.
abstract: 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 (FTalpha/GGT alpha). Elevated expression level of H-ras in myeloma cells, rather than N-ras or FTalpha/GGTalpha, 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.
authors.affiliation: Division of Laboratory Medicine, Department of Adult Hematology & Oncology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA. plzhang@geisinger.edu
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
authors.forename: Albert T
authors.initials: AT
authors.lastname: Quiery
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Blasick
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D004164:Diphosphonates / Q000627:therapeutic use*; D051231:Farnesyltranstransferase / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007150:Immunohistochemistry; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy*; D000077268:Pamidronate; D010414:Pennsylvania; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D000077211:Zoledronic Acid; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000077268:Pamidronate