Cyclin D1 amplification in multiple myeloma is associated with multidrug resistance expression.

BACKGROUND: Cyclin D1 is involved in normal regulation of the cell cycle and in neoplasia. Inhibition of cyclin D1 function markedly attenuates the proliferation of fibroblasts of colon, esophageal, lung, and pancreatic cancer. However, the prognostic value of overexpression of cyclin D1 in multiple myeloma is still a point of debate. This study aimed at evaluating the effect of cyclin D1 gene amplification in multiple myeloma on overall survival and response to therapy. PATIENTS AND METHODS: Fifty patients with multiple myeloma were retrospectively studied. Cyclin D1 gene amplification was studied in bone marrow biopsies of these patients using FISH. An immunohistochemical study of the bone marrow biopsies was done to detect MDR1 protein expression. The correlations between the cyclin D1 gene amplification and overall survival and MDR1 expression were studied and analyzed statistically. RESULTS: Cyclin D1 gene amplification was found in 20% of myeloma patients and was associated with higher percentage of plasma cell infiltration of the bone marrow and increased liability for multiple osteolytic lesions. Cyclin D1-positive patients had a significantly lower progression-free and overall survival and higher levels of MDR1 compared with cyclin D1-negative patients. Cyclin D1 levels showed a highly statistically significant positive correlation with MDR1 levels (R, 0.8 and P < .0001). CONCLUSION: We suggest that there is an association between cyclin D1 gene amplification and disease severity, unfavorable prognosis, and increased expression of MDR1 in multiple myeloma patients.

Increased circulating red cell microparticles (RMP) and platelet microparticles (PMP) in immune thrombocytopenic purpura.

UNLABELLED: It has been suggested that patients with ITP have an increased thrombotic risk compared to the general population and compared to those with other causes of acquired thrombocytopenia. The pro-coagulant role of microparticles in some clinical situations has been reported, yet, very little data is available about microparticles in ITP and their effect. AIM OF THE WORK: To assess the levels of red cell microparticles (RMP), platelet microparticles (PMP) and their possible relation to some haemostatic parameters in ITP patients PATIENTS AND METHODS: The levels of RMP and PMP in addition to FVIII, FIX, FXI, PC and aPTT were assessed in 29 patients with chronic ITP (8 of them had splenectomy). Ten apparently healthy volunteers served as controls. We compared the levels of the studied parameters in ITP patients with that in controls. Correlations of these parameters with each other and with the platelet count were studied. RESULTS: RMP (p=0.0001), PMP (p=0.0001), D- dimer (p=0.048), FVIII (p=0.049), FIX (p=0.0001) and FXI (p=0.0001) were significantly higher in ITP patients compared to controls. aPTT was significantly longer in ITP patients (p=0.0001) but PC showed no significant difference. However, RMP was associated with shorter aPTT. Generally, the coagulation factors were negatively correlated with platelet count in ITP patients. Compared to controls, ITP patients preserved higher levels of RMP and PMP even in those with near-normal platelet count. Splenectomy was associated with lower FIX (p=0.0001) and FXI (p=0.028) and higher RMP (p=0.0001). IN CONCLUSION: Chronic ITP was associated with increased levels of RMP and PMP. FVIII, FIX and FXI were increased in ITP patients but showed a negative correlation with platelet count. Splenectomy was associated with increased levels of RMP and lower levels of FIX and F XI. The high level of microparticles in ITP might point towards a prothrombotic tendency.

Hepatitis C virus-associated thrombocytopenia is not related to serum thrombopoietin levels.

OBJECTIVE: Hepatitis C virus (HCV) infection is one of the most important health problems in Egypt. Thrombocytopenia is a common finding in subjects with chronic hepatitis. The precise etiology of this thrombocytopenia is still obscure. There is increasing interest in the potential role of thrombopoietin (TPO) as a cause of this thrombocytopenia. The aim of this work was to determine serum TPO levels in HCV-positive patients and to test the assumption that HCV-associated thrombocytopenia could be due to low TPO levels. MATERIALS AND METHODS: Forty patients with HCV infection were included in this study and classified into three groups according to the degree of thrombocytopenia (IA-mild, IB-moderate, II-none). Twenty five healthy volunteers served as control (Group III). All patients and controls had undergone full clinical assessment and the following laboratory investigations: complete blood count, liver function tests, prothrombin time and concentration and serum TPO level. RESULTS: TPO levels were significantly elevated in Group IA as compared to the control group ( P <0.05). No significant difference was found between groups IA and II. TPO in Group IB was slightly, but insignificantly reduced compared to Group IA but did not differ statistically from the control or Group II. Significant negative correlation was found between serum TPO levels and platelet counts in Groups IA, IB and II (r=-0.421, P <0.05). No correlations were found between serum TPO levels and liver function tests or hematological parameters. CONCLUSION: An impaired TPO production did not explain the development of thrombocytopenia in HCV and other mechanisms must be involved.