Expression of the chemokine receptors CXCR4 and CCR7 and disease progression in B-cell chronic lymphocytic leukemia/ small lymphocytic lymphoma.
OBJECTIVE
To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL).


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, CCR5, 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 II disease, 2 had stage III disease, and 8 had 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 IV 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).


CONCLUSIONS
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.
Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.
Irene M
IM
Ghobrial
Nancy D
ND
Bone
Mary J
MJ
Stenson
Anne
A
Novak
Karen E
KE
Hedin
Neil E
NE
Kay
Stephen M
SM
Ansell
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D015536:Down-Regulation; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008206:Lymphatic Diseases / Q000378:metabolism; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000378:metabolism; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019707:Receptors, Chemokine / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1