engleski

Higher expression of survivin, akt-1, p53 and bcl-2 in lymph nodes compared to peripheral blood and bone marrow in B-cell chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by clonal expansion and slow but progressive accumulation of monoclonal CD5+CD19+ B lymphocytes which accumulate in peripheral blood, bone marrow and lymphoid organs due to imbalance between birth and death rates. It was shown that circulating B-CLL cells are mostly suspended in G0/G1 phase of cell cycle which leads to the conclusion that accumulation of B-CLL cells is caused by defective cell death signaling which increases the cell survival. However, aggregation of proliferating cells was shown in pseudofollicles of lymph nodes and scattered throughout bone marrow. Because of that fact we examined expression of several key factors regulating proliferation and apoptosis in B-CLL in different microenvironments. Aims. In this study we aimed to analyze and compare difference in expression of proliferation and apoptosis markers on B-CLL cells taken from different microenvironments, i.e. peripheral blood, bone marrow and lymph nodes. Methods. Peripheral blood (PB), bone marrow (BM) and lymph nodes (LN) samples from cases of 25 B-CLL patients, representing major compartments in B-CLL, were taken by conventional techniques. On the same day we analyzed CD5+CD19+ cells for the expression of survivin, p53, bcl-2, Akt-1 and Ki-67 using flow cytometry. We expressed results as percentage of positive cells and mean fluorescence intensity (MFI). Results were statistically analyzed by pair tests. Samples were taken from 25 typical B-CLL patients with mean age of 69 years, 14 males and 11 females. Mean beta-2 microglobulin was 4.65 mg, mean TTM was 9.76, with 24% of patients with lymphoma like tumor distribution (TD<0.5). There were 10, 10 and 5 patients in Binet stages A, B and C respectively. Median expression of survivin was (MFI) 1.44, 1.19 and 2.15 for PB, BM and LN respectively (p<0.05), median expression of bcl-2 was (MFI) 3.13, 3.21 and 3.98 for PB, BM and LN respectively (p<0.05), median expression of p53 was (MFI) 0.24, 0.29 and 0.51 for PB, BM and LN respectively (p<0.05), median expression of Akt-1 was (MFI) 1.03, 1.27 and 1.90 for PB, BM and LN respectively (p<0.05) and median expression of Ki-67 (MFI) was 1.17, 1.01 and 1.79 for PB, BM and LN respectively (p<0.05). MFI values correlate with values expressed as percent of positive cells. Expression of all analyzed markers was highest in LN compared to PB and BM including marker of proliferation Ki-67. We found significantly highest expression of all examined markers in LN compared to PB and BM. This is in line with other results (including expression of CD38 and ZAP-70) indicating higher activity of B-CLL cells in lymph nodes.

B-cell chronic lymphocytic leukemia; Survivin; Akt-1; P53; Bcl-2

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