Expression of the Chemokine Receptors CXCR4 and CCR7 and Disease Progression in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Ghobrial, Irene M.; Bone, Nancy D.; Stenson, Mary J.; Novak, Anne; Hedin, Karen E.; Kay, Neil E.; Ansell, Stephen M.
March 2004
Mayo Clinic Proceedings;Mar2004, Vol. 79 Issue 3, p318
Academic Journal
• Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL)., • Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15,1991, and February 7,2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 , CCR2, CCR4, CCRS, CCR6, and CCR7) and also to CD19. • Results: Of the 45 patients in this study, 20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage H disease, 2 had stage HI disease, and Shad stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage Pt compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and P<001, respectively). • Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemokine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.


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