CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease.
The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked to an overexpression of the chemokine receptor CXCR4 and increased in vitro functional response to its natural ligand CXCL12 (SDF-1). The CXCR4/SDF-1 system appears to be important for tissue localization and increased survival of B-CLL cells. The aim of our study was to examine if CXCR4 expression and SDF-1 blood levels were correlated to clinical and pathological stage of B-CLL. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to determine CXCR4 expression and SDF-1 plasma levels, respectively, in a cohort of 51 patients diagnosed with B-CLL to correlate these measurements with several parameters that define the clinical stage of the disease. We confirmed that CXCR4 was consistently expressed on circulating B-CLL cells with a fluorescence intensity that was five-fold greater than in cells from healthy volunteers. There was a correlation between CXCR4 expression and leukocyte count ( r: 0.55, p<0.01), and CD19(+)/CD5(+ )cells ( r: 0.63, p<0.01). Interestingly, the group of B-CLL patients showed lower SDF-1 plasma levels compared to the control group. However, there was no correlation between CXCR4 or SDF-1 expression and the clinical stage of disease or the pattern of bone marrow infiltration. The results obtained suggest that other factors, and not only alteration in the SDF-1/CXCR4 chemokine system, must account for marrow infiltration of neoplastic cells observed in B-CLL and that CXCR4 could be involved in other features that exhibit malignant B cells, such as increased survival, rather than in their homing or migration to the bone marrow.
Barretina
J
J
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Juncà
J
J
Hematology Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Llano
A
A
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Gutiérrez
A
A
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Flores
A
A
Hematology Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Blanco
J
J
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Clotet
B
B
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
Esté
J A
JA
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. jaeste@ns.hugtip.scs.es.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019718:Receptors, CXCR4 / Q000378:metabolism*
C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015851:Interleukin-7; D019718:Receptors, CXCR4