title: Dual role of the CXCL12 polymorphism in patients with chronic lymphocytic leukemia.
abstract: The CXCL12 [chemokine (C-X-C motif) ligand 12] is a member of the CXC family of chemokines and interacts with its CXCR4 receptor. The CXCL12/CXCR4 axis is involved in regulation of proliferation, survival and trafficking of hematopoietic stem cells, including B lymphocytes and disruption within this signaling pathway has been implicated in pathogenesis of chronic lymphocytic leukemia (CLL). The aim of this study was to determine a potential association of the CXCL12 rs1801157 G > A polymorphism with susceptibility to CLL, the disease course and efficacy of therapy. Also, expression of the CD74 and CD38 proteins on B cells was analyzed in relation to clinical parameters and genotyping results. A total of 124 patients with CLL and 75 healthy controls were studied. CXCL12 genotyping was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. The CD74 and CD38 surface expression was determined using flow cytometry. There was a significantly increased frequency of the A allele and AA genotype in CLL patients compared with control group (P < 0.001 in both cases). In addition, the A allele was overrepresented among patients with worse response to therapy in comparison to other genotypes (P < 0.001). On the contrary, patients carrying the A allele displayed lower grade of the disease at diagnosis more frequently than patients homozygous for the G allele (P = 0.037). Moreover, the AA homozygosity correlated with lower CD74 expression on B cells (P = 0.007). In conclusion, data from this study indicate that the CXCL12 rs1801157 G > A polymorphism may affect CLL development, disease progression as well as response to treatment.
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.|Department of Physiology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Butrym
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Gebura
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Iwaszko
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.|Department of Internal, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Department of Internal, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Mazur
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; C045084:invariant chain; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: CD74; CXCL12; SDF-1; chronic lymphocytic leukemia; gene polymorphism