title: Stromal cell-derived factor-1 chemokine gene variant in blood donors and chronic myelogenous leukemia patients.
abstract: Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell expressing the bcr-abl oncogene. It is characterized by an abnormal release of the expanded, malignant stem cell clone from the bone marrow into the circulation. The stromal cell derived factor-1 (SDF-1) gene contains a common polymorphism, termed SDF1-3'A, in an evolutionarily conserved segment of the 3' untranslated region (UTR). In this work the SDF-1 genotypes of 25 patients (9-82 years old) who had been clinically and hematologically diagnosed with CML were compared with those of 60 healthy donors. In addition, the nature of bcr-abl hybrid mRNA and the association between demographic and hematological parameters were analyzed in cells from 12 CML patients (five women and seven men). All patients underwent blood collection during the chronic phase of disease after they received chemotherapy. b3a2 mRNA was detected in samples from eight of the CML patients and b2a2 mRNA was observed in four cases. An association between basophils and hemoglobin parameters was observed in that hemoglobin levels were higher in b2a2-expressing patients, and mean basophil levels were higher in patients expressing b3a2. Four of the CML patients (16%) were homozygous for 3'A allele. Of the patients who showed the presence of bcr-abl transcripts (N = 12), three presented the wt/wt genotype and nine were SDF1-3'A carriers. Three of the latter were homozygous for this mutation. It is possible that the bcr-abl fusion gene and the SDF1 genotype for 3'A allele have important implications for the pathogenesis of CML.
authors.affiliation: Department of Pathological Sciences-Immunology-Genome, Biological Sciences Center, Londrina State University, Londrina, Brazil.
authors.forename: Carlos Eduardo Coral
authors.initials: CE
authors.lastname: de Oliveira
authors.forename: Gabriela Gonçalves de Oliveira
authors.initials: GG
authors.lastname: Cavassin
authors.forename: Aparecida de Lourdes
authors.initials: Ade L
authors.lastname: Perim
authors.forename: Thiago Franco
authors.initials: TF
authors.lastname: Nasser
authors.forename: Karen Brajão
authors.initials: KB
authors.lastname: de Oliveira
authors.forename: Maria Helena Pelegrinelli
authors.initials: MH
authors.lastname: Fungaro
authors.forename: Juliana Laino do Val
authors.initials: JL
authors.lastname: Carneiro
authors.forename: Maria Angelica Ehara
authors.initials: MA
authors.lastname: Watanabe
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001782:Blood Donors; D016022:Case-Control Studies; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D002648:Child; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D020413:3' Untranslated Regions; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C406060:abl-bcr fusion protein, human; D016044:Fusion Proteins, bcr-abl