RESUMEN
As at present only a long-term follow-up can fully determine whether monoclonal gammapathies of undetermined significance (MGUS) will evolve into multiple myeloma (MM), this study attempted to identify other variables connected with the amount of monoclonal component (MC), generally considered as the most reliable marker of malignant evolution. Thirty-four MGUS subjects showing a high MC (> or = 15.0 g/l) but without clinical evidence of MM (MGUS group b), were characterized for their phenotypic and genotypic profile by comparing them either with 40 MM patients or with 24 subjects affected by a benign form of monoclonal gammapathy (MGUS group a) according to the standard criteria. In addition to the usual laboratory markers, the levels of expression of a panel of CD membrane subsets were measured on B and T lymphocytes. Also, the serum level of the p53 mutant protein and the structural alterations of the c-myc oncogene were evaluated. The results show that for MGUS group b patients, an increased M-protein was accompanied by significantly increased levels of peripheral blood CD3+ T cells and oncogenetic aberrations in c-myc. Since a high serum MC level seems to indicate a greater likelihood of malignant transformation for MGUS patients, these findings suggest that this relationship may be a result of the concomitant alterations observed at a phenotypic and genotypic level. Such alterations may be potentially useful as surrogate markers for the transition of benign to malignant (MM) plasma cell dyscrasia.
Asunto(s)
Marcadores Genéticos , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Mieloma Múltiple/genética , Paraproteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Southern Blotting , ADN de Neoplasias/análisis , Progresión de la Enfermedad , Femenino , Genes myc/fisiología , Genotipo , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/diagnóstico , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Transformación GenéticaRESUMEN
PURPOSE: To determine the role of serum levels of IL-6 and p53 mutant protein as well as of c-myc proto-oncogene alterations: a) in discriminating between benign (MGUS) and malignant Plasma cell dyscrasias (Multiple and Microsecreting Myeloma, Plasmocytoma); b) in monitoring the clinical course of malignant forms of this disease. PATIENTS AND METHODS: Eighty-eight patients affected by Plasma cell dyscrasias (58 MGUS, 24 MM and 6 PLC) entered this study. Using commercially available ELISA kits, serum levels of IL-6 and p53 have been determined in all the patients. In addition, a selected group of patients (n = 30) was also analyzed for structural c-myc gene alterations by Southern blot technique. RESULTS: The results show that, conversely from p53 protein, IL-6 and c-myc gene may represent useful diagnostic markers for discriminating benign from malignant forms of Plasma cell dyscrasia. On the contrary, preliminary findings of the same work indicate a potential role for the mutant p53 protein in monitoring the response to chemotherapy of patients affected by MM or PLM. CONCLUSIONS: Overall, these data suggest that the combined use of IL-6, p53 and c-myc may provide a new approach for a more rational management of Plasma cell dyscrasia patients.
Asunto(s)
Biomarcadores de Tumor , Interleucina-6/sangre , Paraproteinemias/diagnóstico , Proteínas Proto-Oncogénicas c-myc/sangre , Proteína p53 Supresora de Tumor/sangre , Adulto , Anciano , Anciano de 80 o más Años , Southern Blotting , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Genes myc/genética , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Paraproteinemias/sangre , Plasmacitoma/sangre , Plasmacitoma/diagnóstico , Proto-Oncogenes MasAsunto(s)
Paraproteinemias/patología , Antígenos CD/análisis , Genotipo , Humanos , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Inmunofenotipificación , Interleucina-6/sangre , Mutación , Paraproteinemias/sangre , Paraproteinemias/diagnóstico , Fenotipo , Pronóstico , Proteínas Proto-Oncogénicas c-myc/genética , Proteína p53 Supresora de Tumor/sangre , Proteína p53 Supresora de Tumor/genética , Microglobulina beta-2/análisisRESUMEN
Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P=0.001) in the treated group, suggesting the activation of reducing mechanisms.