engleski

ZAP-70 has higher expression in lymph nodes and bone marrow compared to peripheral blood in B-cell chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable clinical presentation and course with variable affection of different lymphoid organ compartments. There is well documented both intraclonal and interclonal variability among B- CLL cells with respect to different microenvironment in major lymphoid compartments as we have previously shown (Jaksic et al, Blood 2004). ZAP-70 molecule with significant role in cell signaling and is very important negative prognostic parameter. However its expression is evaluated mainly in peripheral blood which is considered as mostly inert compartment compared to bone marrow and lymph nodes where proliferative centers were documented fueling B-CLL proliferation and progression. Aims were to evaluate whether there is difference in ZAP-70 expression in B-CLL lymphocytes associated with distinct microenvironment in major lymphoid compartments. Samples from peripheral blood (PB), bone marrow (BM) and lymph nodes (LN) representing major compartments in B-CLL were taken on the same day by conventional technique. We have measured the expression of ZAP-70 by flow cytometry by previously published method using ZAP-70, CD3, CD56, CD5 and CD19 markers (Letestu, Cytometry 2006). ZAP-70 expressions was expressed as percentage of ZAP-70 positive B-CLL cells according to ZAP-70 expression in T-lymphocytes (%/T-Ly) and as T/CLL mean fluorescence intensity (MFI) ratio. Results were analyzed by paired tests. Samples were taken from 42 typical B-CLL patients, median age was 70yr, there were 55% males, mean beta-2 microglobulin was 3.9 mg, mean TTM was 9.3, there were 22% of patients with lymphoma-like tumor distribution (TD<0.5). There were 17, 16 and 8 patients in Binet stages A, B and C respectively. ZAP-70 expression as T/CLL ratio (mean ± ; s.d.) was 4.9± ; 3.7, 2.9± ; 2.1 and 1.7± ; 0.8 for PB, BM and LN respectively (p<0.00001). Results for percentage of positive B- CLL cells (%/T-Ly) were at the same level of statistical significance (p< 0.00001) with median percentage in PB 19.7%, in BM 62.3% and in LN 92.9% showing the lowest expression in peripheral blood and the highest expression in lymph nodes. We have shown that B-CLL lymphocytes taken from different lymphoid compartments have significantly different ZAP-70 expression supporting the importance of lymph node and bone marrow compartments in B-CLL pathogenesis.

ZAP-70; chronic lymphocytic leukemia; expression

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