Stromal cell-derived factor-1 chemokine gene variant in blood donors and chronic myelogenous leukemia patients

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.