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Cytobiological studies in multiple myeloma.

Abstract

Multiple myeloma (MM) is a heterogeneous disease in which the median survival time varies from a few months to more than 10 years. Clinical, kinetic, and immunological studies reflected such a heterogeneity. In clinical studies beta 2-microglobulin (beta 2-M), which is a well-known prognostic factor, was evaluated as an expression of tumor burden: a linear increase has been observed from stage I to stage III. No clear cutoff was detected between monoclonal gammopathy of undetermined significance (MGUS) and stage I MM. Kinetic studies have been performed by 3[H]thymidine or 5-bromo-2-deoxyuridine incorporation in bone marrow plasma cells. An analysis has been carried out between beta 2-M and the labeling index (LI). No correlation has been observed between these 2 parameters which identify different subgroups of poor prognosis patients. MGUS always showed an LI less than 1% allowing a clear distinction from stage I MM. A reduced survival time has been observed in patients with an LI greater than 2%. A subgroup of MM patients characterized by an LI greater than 2% and a decrease of M component greater than 50% within 3 months (early responders) has been identified. These patients showed a median survival time of about 10 months. Immunological studies identified a sharp decrease of 5' nucleotidase (5'NT) enzymatic activity in peripheral blood lymphocytes. This enzymatic defect is the biochemical marker of the expansion of a T subpopulation expressing low levels of 5'NT. This subpopulation was characterized by monoclonal antibodies and is represented by activated suppressor cells (OKM1+, DR+). Such an unbalancement in the T cell subpopulation was evident in poor prognosis patients. Clinical, kinetic and immunological studies identified new prognostic parameters that will be useful in the future therapeutic strategy of MM.

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BibTeXRIS

A Pileri, M Massaia, U Dianzani, P Omedè, M Boccadoro. 1987. Cytobiological studies in multiple myeloma.. https://doi.org/10.1159/000205901

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5'-Nucleotidase↗

Nucleotide metabolizing ecto-enzymes in Walker 256 tumor cells: molecular identification, kinetic characterization and biochemical properties.

In this study we describe the molecular identification, kinetic characterization and biochemical properties of an E-NTPDase and an 5'-nucleotidase in Walker 256 cells. For the ATP, ADP and AMP hydrolysis there were optimum pH in the range 6.5-8.0, and absolute requirement for divalent cations (Mg(2+)>Ca(2+)). A significant inhibition of ATP and ADP hydrolysis was observed in the presence of high concentrations of sodium azide and 0.5 mM of Gadolinium chloride. These activities were insensitive to ATPase, adenylate kinase and alkaline phosphatase classical inhibitors. The K(m) values were 464.2+/-86.6 microM (mean+/-SEM, n=4), 137.0+/-31 microM (mean+/-SEM, n=5) and 44.8+/-10.2 microM (mean+/-SEM, n=4), and V(max) values were 655.0+/-94.6 (mean+/-SEM, n=4), 236.3+/-27.2 (mean+/-SEM, n=5) and 177.6+/-13.8 (mean+/-SEM, n=5) nmol of inorganic phosphate min(-1) mg of protein(-1) for ATP, ADP and AMP, respectively. Using RT-PCR analysis we identified the mRNA of two members of the ecto-nucleoside triphosphate diphosphohydrolase family (NTPDase 2 and 5) and a 5'-nucleotidase. The presence of NTPDases and 5'-nucleotidase enzymes in Walker 256 tumor cells may be important to regulate the ratio adenine nucleotides/adenine nucleoside extracellularly, therefore motivating tumor growth.

5'-Nucleotidase↗

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5'-Nucleotidase↗