The prognostic role of CXCR3 expression by chronic lymphocytic leukemia B cells.
OBJECTIVE
Chemokine receptors are involved in tumor progression and several of these receptors, including CXCR3, are expressed by chronic lymphocytic leukemia (CLL) B cells. This study was aimed to examine a possible relationship between CXCR3 expression in CLL and the clinical evolution of the disease.


METHODS
Using flow activated cell sorting (FACS), we analyzed the level of expression of CXCR3 on blood CLL B cells from 76 consecutive patients. The results were correlated with CD38 expression, IgVH gene status and clinical outcome.


RESULTS
CXCR3, measured as mean fluorescence intensity (MFI), was unimodally expressed by blood tumor cells at various levels (range, 3.5 to 232.3) but levels within individual patients were remarkably stable over time. Low CXCR3 expression by CLL B cells was strongly associated with Rai disease stages III and IV (p<0.0001) and a pattern of diffuse tumor infiltration of the bone marrow (p<0.0001). In the 28 cases available for genetic studies, low CXCR3 expression also showed good concordance with tumor unmutated IgVH gene status (p<0.04), and tended to correlate with high CD38 expression (p<0.06). Patients with low CXCR3 expression (MFI < or =15) had a shorter survival (p<0.0001) and, in multivariate analysis, low CXCR3 expression (MFI pound15) was an independent predictor of poor outcome (hazard ratio 24.5; p<0.01). INTERPRETATION AND CONCLUSIONSL: CXCR3 expression by CLL B cells appears to be stable within individual patients. Tests to assay this chemokine receptor are cheap and easy to perform and the results could be of prognostic value in CLL.
Ocaña
Esther
E
Servicio de Inmunología and Unidad de Investigación, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Delgado-Pérez
Luis
L
Campos-Caro
Antonio
A
Muñóz
Juan
J
Paz
Antonio
A
Franco
Rafael
R
Brieva
José A
JA
D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C515187:CXCR3 protein, human; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1