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Different CXCR4, CXCR3, CXCR5, CCR7 and Ki-67 expression in peripheral blood, bone marrow and lymph nodes in B-cell chronic lymphocytic leukemia (B-CLL)

1. Background: B-cell chronic lymphocytic leukemia has highly variable clinical presentation and course with variable involvement of different lymphoid compartments which translates into variable tumor distribution. Important role in lymphocyte trafficking and homing have adhesion molecules and chemokine receptors. We have previously shown that there is significant variability regarding adhesion molecule expression between lymphoid compartments with significant association with clinical presentation and course (Jaksic et al, Blood 2002). Important role in trafficking and homing as well as regulation of expression of adhesion molecules have been documented in in vitro models for chemokine receptors. This points to need to evaluate whether there is an intraclonal variability due to distinct microenvironment in vivo, as well as whether different chemokine receptor profile correlates with cell proliferations. 2. Aims: to evaluate and compare the expression of various chemokine receptors as well as marker of proliferation Ki-67 on B-CLL lymphocytes taken from various lymphoid compartments, ie peripheral blood (PB), bone marrow (BM) and lymph nodes (LN). 3. Methods: samples were taken from peripheral blood (PB), bone marrow (BM) and lymph nodes (LN) representing major compartments in B-CLL, by conventional techniques on the same day. We have measured expression of CXCR3, CXCR4, CXCR5, CCR7 and Ki-67 on CD5+CD19+ cells by flow cytometry and we have expressed the results as percentage of positive cells and mean fluorescence intensity (MFI). Results were analyzed by paired tests. 4. Results: samples were taken from 21 typical B-CLL patients (median age 69 years, males 56%). Mean beta-2 microglobulin was 4.5 mg, mean TTM was 10.3, with 35% of patients with lymphoma-like tumor distribution (TD <0.5). There were 7, 10 and 4 patients in Binet stages A, B and C respectively. Median CXCR3 expression was 15.8, 9.7 and 17.3% for PB, BM and LN respectively (p<0.01 PB and LN vs. BM). Median CXCR4 expression was 51, 17 and 12.3% for PB, BM and LN respectively (p<0.01 PB vs. BM and LN)). Median CXCR5 expression was 94.1, 87.7 and 64.5% for PB, BM and LN respectively (p<0.01 PB and BM vs. LN). Median CCR7 expression was 98.2, 96.6 and 72% for PB, BM and LN respectively (p<0.01 PB and BM vs. LN). Mean Ki-67 expression (MFI) 0.89, 0.76 and 1.39 for PB, BM and LN respectively (p<0.01 PB and BM vs. LN). CXCR4 expression was higher in PB compared to BM and LN, CXCR3 expression was lower in BM then in PB and LN, CXCR5 and CCR7 expression was higher in PB and BM compared to LN. Ki-67 expression was highest in lymph nodes. 5. Summary / Conclusions: There is a significant intraclonal variability for several chemokine receptors regarding different lymphoid compartments. This chemokine receptor profile inversely correlates with proliferative status of B-CLL cells in respective compartments.

B-cell chronic lymphocytic leukemia; CXCR4; CXCR3; CXCR5; CCR7; Ki-67; expression

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