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.

Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

“…Previous studies have shown that a variety of morphological and functional abnormalities exist in the leukemia bone marrow microenvironment, including significantly increased microvascular density, increased expression of some vascular-related growth factors such as VEGF, and some chemokines such as SDF-1 (10,13,14). The disturbance of the leukemia bone marrow microenvironment could promote the production of abnormal adhesion molecules and chemokines, which in turn could promote the adhesion and colonization of leukemia cells to the "niches" of the local microenvironment, thus allowing the leukemia cells to evade chemotherapy through the shielding role of the local hematopoietic matrix.…”

Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors

“…Of note, the CXCL12-801A allelic variant has been associated with a higher incidence of breast and lung cancer, acute myeloid leukemia, lymphoma and chronic myeloproliferative disease, and with a slower progression to AIDS. 31,[34][35][36][37][38] An interaction between CXCL12 and CXCR4 is critical for the trafficking of hematopoietic progenitor cells in the BM, and an interruption of this interaction can affect…”

Prognostic Importance of Single-Nucleotide Polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α Genes in Chronic Phase Chronic Myeloid Leukemia

“…Previous studies have shown that polymorphisms in regulatory regions of cytokine genes could affect transcription, resulting in variations of cytokine protein production. Recently, the association between cytokine genes and leukemias has been examined intensively (Bidwell et al, 2001;De Oliveira, 2007).…”