sodium-bisulfite and Multiple-Myeloma

We analysed the clinical impact of epigenetic dysregulation of the Wnt pathway in malignant plasma cell disorders. In multiple myeloma (MM) cell lines, aberrant promoter hypermethylation of the secreted Frizzled-related protein (SFRP) genes was a common event, and hypermethylation of SFRP1,-2 and -5 was associated with transcriptional silencing. Among 76 primary patient samples, the frequency of aberrant methylation was 35.5% for SFRP1, 52.6% for SFRP2, 1.3% for SFRP4 and 6.9% for SFRP5. Hypermethylation of SFRP1 and -2 genes was detected in monoclonal gammopathy of undetermined significance and all MM stages including plasma cell leukaemia (PCL), while SFRP5 methylation was restricted to advanced MM stages and PCL. Our data indicate that epigenetic silencing of Wnt antagonists is an early event in MM pathogenesis and that SFRP5 hypermethylation may play a role in disease progression.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Cell Line, Tumor; CpG Islands; DNA Methylation; DNA, Neoplasm; Epigenesis, Genetic; Eye Proteins; Female; Humans; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Leukemia, Plasma Cell; Male; Membrane Proteins; Middle Aged; Multiple Myeloma; Neoplasm Proteins; Promoter Regions, Genetic; Proto-Oncogene Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sulfites; Survival Analysis; Wnt Proteins

A model of a stepwise malignant transformation has been proposed for the pathogenesis of monoclonal gammopathies. In this model, cell cycle regulators play a central role as a source of genetic events; particularly, p16/INK4a gene acts as a tumoral suppressor gene and, recently, inactivation of this gene through a methylation mechanism, has been observed in multiple myeloma patients. Under the diagnosis of monoclonal gammopathies there is a broad spectrum of disorders with very different outcomes, ranging from indolent courses, such as those of monoclonal gammopathy of undetermined significance, Waldeströn macroglobulinemia and smoldering multiple myeloma, to aggressive diseases such as symptomatic MM and primary plasma cell leukemia. To the best of our knowledge, the activity of p16 gene has not been evaluated and compared in these different subtypes of monoclonal gammopathies.. The methylation status of the p16 gene was analysed in a group of 159 patients with monoclonal gammopathies (40 monoclonal gammopathy of uncertain significance, eight Waldenström Macroglobulinemia, eight smoldering multiple myeloma, 98 symptomatic multiple myeloma and five primary plasma cell leukemia) using three different assays (restriction enzymes and PCR or S-B and modification by sodium bisulphite).. Forty-one of 98 MM patients (41.8%) as well as four of the five (80%) primary PCL patients showed methylation of the p16 gene, while none of the patients with monoclonal gammopathy of undetermined significance, Waldenström Macroglobulinemia or smoldering multiple myeloma displayed a methylation status.. These findings suggest that the methylation of the p16 gene could be a relevant oncogenic event in the monoclonal gammopathies evolution being associated with the most aggressive forms.

Topics: Cyclin-Dependent Kinase Inhibitor p16; Disease Progression; DNA; DNA Methylation; DNA, Neoplasm; Gene Silencing; Genes, p16; Leukemia, Plasma Cell; Multiple Myeloma; Neoplasm Proteins; Paraproteinemias; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sulfites; Waldenstrom Macroglobulinemia

To report a case of seizures occurring during administration of high-dose intravenous morphine containing sodium bisulfite as a preservative.. A 56-year-old woman hospitalized with multiple myeloma developed myoclonic and tonic-clonic seizures following administration of intravenous morphine with sodium bisulfite preservative at doses exceeding 400 mg/h. These seizures resolved when the morphine was discontinued, anticonvulsants were administered, and the drug therapy was changed to intravenous fentanyl without preservative.. The factors potentially associated with this adverse reaction are discussed and the literature concerning the adverse central nervous system effects of opiates and sulfites is reviewed.. High doses of intravenous morphine with sulfite preservative may be associated with seizure development. If patients require high doses of intravenous morphine, a preservative-free formulation should be used to avoid possible additive or synergistic toxicities.

Topics: Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Female; Humans; Infusions, Intravenous; Middle Aged; Morphine; Multiple Myeloma; Pain, Intractable; Preservatives, Pharmaceutical; Sulfites