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Background. The PIM2 gene belongs to the PIM family, which encodes serine/threonine kinases involved in cell survival and apoptosis. The relation between the expression of the PIM2 gene and the course of chronic lymphocytic leukemia (CLL) has not been fully determined. Objectives. The aim of the study was to evaluate the role of the PIM2 gene as a marker of CLL malignancy and its importance as a predictive and prognostic factor. Material and methods. Sixty-seven patients, 35 females and 32 males, aged 49-90 years, with de novo CLL, and 14 healthy individuals were enrolled in the study. Expression of the PIM2 gene was analyzed using TaqMan RQ-PCR assay and western blot test. Results. Median PIM2 gene expression in CLL patients was higher than in controls. Patients with high expression of the PIM2 gene had shorter progression-free survival and time to first treatment than patients with low PIM2 expression. It was found that patients with CR had lower expression of the PIM2 gene than patients without complete remission (CR). Notably, associations between high PIM2 expression and rapid lymphocyte doubling time, the percentage of malignant lymphocytes with ZAP70 expression and the Rai stage were revealed. Conclusions. We found that the PIM2 gene is associated with a more aggressive clinical course of CLL. [ABSTRACT FROM AUTHOR]

Background. Graves' orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is characterized by dramatic tissue reactivity. Both inflammation and tissue remodeling characterize the clinical course of GO. Some data has been found regarding the association of MMPs and TIMPs in GO. Material and methods. Serum concentrations of MMP-9, MMP-2, TIMP-1, and TIMP-2 were determined by ELISA method. Objectives. Forty-eight patients (34 females, 14 males, with median age 51.5 years) with GD and hyperthyroidism were enrolled in the study. In 28 patients, active, moderate-to-severe grade orbitopathy was diagnosed. The aim of this study was to assess the serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 in patients with Graves' disease (GD), with and without GO, and their relationship with disease severity, as well as to evaluate how these concentrations change after successful treatment. Results. Median serum concentrations of MMP-2 and MMP-9 were significantly higher in all patients with GD as well as in the subgroup with GO than in the control group. Median serum concentrations of TIMP-1 and TIMP-2 were significantly higher in all patients with GD than in controls. The same significant differences were observed in the subgroups with and without GO in comparison with controls. The GO subgroup showed a significant positive correlation between the MMP-9 concentration and the serum level of TSHRAb antibodies, and a clinical activity score =4 according to EUGOGO. Conclusions. In our study we found that only MMP-9 differentiates the patients with and without GO, and may be used as a marker of the disease severity in patients with this manifestation of GD. [ABSTRACT FROM AUTHOR]

Introduction: PIM-2 is a protooncogene that encodes for a serine/threonine kinase that interacts with various signaling molecules. PIM-2 is highly expressed in neoplastic tissues and in leukemic and lymphoma cell lines, which is consistent with its role during oncogenic transformation. The nuclear factor kappa B (NF-κB) pathway appears to be deregulated in a variety of tumors, with sustained activity of NF-κB leading to apoptotic resistance in tumor cells. The aim of this study was to investigate whether expression of PIM-2 and NF-κB is altered in acute myeloid leukemia (AML) and acute lmyphoblastic leukemia (ALL). Patientsand methods:One hundred fortythree patients were included: 91 with AML and 52 with ALL, aged 18-84 (median 46.7). Eightythree patients (51 AML and 32 ALL) reached complete remission (CR). Bone marrow samples were collected at the time of diagnosis. Control samples were obtained from 24 healthy donors. We analyzed PIM-2 and NF-κB expression by RQ-PCR analysis. Results:Expression of both PIM-2 and NF-κB genes in all leukemic patients and both subgroups AML and ALL was significantly higher than in controls. AML patients who reached CR expressed PIM-2 and NF-κB at significantly lower levels than patients with primary resistance to chemotherapy who did not reach CR (NCR). Survival analysis revealed that in AML patients, higher expression of PIM-2 was related to significantly shorter patients' overall survival (OS). Conclusion: Our data indicate that increased expression of PIM-2 and NF-κB genes may be involved in patho-genesis of AML and ALL. Moreover, high PIM-2 expression could be associated with CR rate and OS in AML patients [ABSTRACT FROM AUTHOR]

Introduction: T cells with the CD8+CD28- phenotype are CD8+ lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8+CD28- lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL) has not yet been described. The aim of the study was to determine their levels in these patients' peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease., Material/methods: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8+CD28- lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates., Results: The percentage of CD8+CD28- lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8+CD28- lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8+CD28- lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8+CD28- T cells in the skin infiltrates correlated positively with age and clinical stage of the disease., Conclusions: These data suggest that CD8+CD28- lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma.

Cyclin-dependent kinases (cdk) play the important role in neoplastic transformation. Their activity depends on interaction with proteins called inhibitors. There are two groups of inhibitors: INK4 (p16INK4a, p15INK4b, p18INK4c, p19INK4d) and proteins p21WAF1/Clip1, p27Kip1, p57Kip2. Alteration of inhibitors expression was assessed in acute lymphoblastic leukemia (ALL) and in acute myeloblastic leukemia (AML), but the results are not clear. The aim of our study was to estimate p16INK4a, p15INK-4b, p21WAF1/Clip1 expression in blast cells in patients with AML and ALL by cytochemistry method and to compare with the result of treatment. Forty-two patients were included in the study, 23 with AML and 19 with ALL. Expression of inhibitors was considered as positive when detected in > 5% of blast cells. Complete remission (CR) rate in patients with positive expression p16INK4a and p15INK4b was statistically significantly higher than in patients with negative expression: for p16INK4a chi 2 = 7.78, p < 0.01, for p15INK4b, chi 2 with Yates' modification = 3.94, p < 0.05. There was no difference in CR rate in patients with positive and negative p21WAF1/Clip1 expression. Moreover the patients with simultaneous expression of three inhibitors reached CR more often than the others: chi 2 = 7.43, p = 0.01 for AML and chi 2 = 6.74, p < 0.01 for ALL. Our study indicates that estimation of p16INK4a, p15INK4b, p21WAF1/Clip1 expression in blast cells can be used as prognostic factor in acute leukemia.

Apoptosis mediated by the interaction of cytotoxic T lymphocyte with blast cell via Fas receptor/Fas ligand (FasL) pathway is a one of the mechanisms of immunological leukemia surveillance. There is few data on possible blocking of Fas receptor by soluble form of Fas (sFasL) present in serum and the role of blast cells as the source of this ligand. Forty-eight patients with de novo diagnosis of acute leukemia, 32 with myeloblastic (AML) and 16 with acute lymphoblastic leukemia (ALL) were studied. Fas expression on bone marrow leukemic blasts was determined by flow cytomertic immunofluorescent analysis and serum concentration of sFasL assessed at presentation, in remission and in relapse. Blasts of all patients expressed Fas at variable degree (0.8 to 100%). Fas expression was significantly higher on myelo--than on lymphoblasts. There was no relation between degree of Fas expression at diagnosis and remission rate. Concentration of sFasL in acute leukemia patients at diagnosis was significantly higher than in healthy control group, decreased to normal values in remission and rose again in relapse. There was a negative correlation between Fas expression on blasts and sFasL concentration at the time of diagnosis. Results obtained suggest that blast cells could be the source of soluble FasL in acute leukemia patients and that sFasL serum concentration could be used for monitoring of disease activity.

Background: Monitoring of disease activity and effectiveness of treatment plays an important role in curative management of patients with non-Hodgkin's lymphomas (n-HL). In the search for markers useful for biochemical monitoring of n-HL patients, a group of proteins called adhesion molecules attracted attention. Particular attention has been devoted to sICAM-1 (intercellular adhesion molecule-1). A correlation between sICAM-1 levels and histological malignancy grades and clinical staging of n-HL, activity of the disease and tumor mass has been observed. The aim of the study was to assess the utility of determining serum levels of selected adhesion molecules in n-HL monitoring. The study was carried out in 60 patients with intermediate and high malignancy grade n-HL according to Working Formulation (anaplastic, lymphoblastic, immunoblastic, centroblastic and centroblastic-centrocytic)., Material/methods: Soluble ICAM-1 adhesion molecule (sICAM-1) and selectin E levels were determined in the sera of 31 newly diagnosed patients, 18 with complete remission, and 11 with relapse of the disease. The control group consisted of 15 healthy subjects. The results were expressed in ng/ml., Results: sICAM1 levels were similar in healthy controls and patients in the remission phase and significantly lower in patients with diagnosed active disease and relapses. Relapses were associated with slightly lower levels (on borderline of statistical significance) than of diagnosis Serum selectin E levels, however, demonstrated no differences among patient groups or as compared with controls., Conclusions: The presented results indicate the utility of serum sICAM-1 level determination in assessment of activity of intermediate and high malignancy grade non-Hodgkin's lymphomas.