title: The CXCL12-3'A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation.
abstract: The interaction between CXCL12 and its receptor CXCR4 plays a crucial role in the homing and mobilization of haematopoietic progenitors. We investigated the putative association between a CXCL12 gene polymorphism, the G --> A transition at position 801 in the 3'-untranslated region (3'UTR), and the yield of CD34(+) progenitors in 65 healthy allogeneic transplant donors who received G-CSF. Importantly, in this setting, the analysis was not biased by background disease or chemotherapy. The 3'UTR CXCL12 G801A polymorphism was detected using a PCR-RFLP technique with the MspI restriction enzyme and the frequency of CD34(+) progenitors was assessed by flow cytometry. The frequency as well as the number of CD34(+) progenitor cells in the first leukapheresis product was significantly higher from donors with the CXCL12-3'A allele compared to GG homozygotes (P<0.05 in both cases), especially for subjects with the CXCL12-3'AA homozygous genotype (P<0.01 in both cases). Moreover, more leukaphereses were needed to obtain the required number of CD34(+) progenitors for transplantation from CXCL12-3'GG homozygous donors compared to the CXCL12-3'A carriers (P=0.003). In conclusion, the CXCL12-3'A allele was associated with a higher yield of CD34(+) cells from healthy donors of PBPC for allogeneic haematopoietic SCT.
authors.affiliation: L Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. bogunia@iitd.pan.wroc.pl
authors.forename: K
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.forename: A
authors.initials: A
authors.lastname: Gieryng
authors.forename: D
authors.initials: D
authors.lastname: Dlubek
authors.forename: A
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018952:Antigens, CD34 / Q000096:biosynthesis*; D001782:Blood Donors; D054377:Chemokine CXCL12 / Q000235:genetics*; D002648:Child; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor