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  • Title: The role of polymorphisms of stromal-derived factor-1 and CXC receptor 4 in acute myeloid leukemia and leukemia cell dissemination.
    Author: Zheng Q, Shuai X, Ye Y, Jin Y, Jiang N, Chen X, Su J.
    Journal: Gene; 2016 Aug 22; 588(2):103-8. PubMed ID: 27154815.
    Abstract:
    BACKGROUND: Acute myeloid leukemia (AML) is a form of cancer characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated cells of the hematopoietic system. Chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXC receptor 4 (CXCR4) play crucial roles in malignant cell invasion. Genetic polymorphisms may contribute to the differences in the expression level and activities associated with the SDF-1/CXCR4 pathway. This study aimed to determine the associations between the polymorphisms located on the SDF-1 (rs1801157, G>A) and CXCR4 (rs2228014, C>T) encoding genes and susceptibility and leukemia cell dissemination in AML. METHODS: A total of 926 individuals, including 466 de novo AML patients and 460 healthy controls were genotyped for rs1801157 and rs2228014 using DNA Sanger sequencing. RESULTS: Genotype distributions of CT and CT+TT for rs2228014 were significantly increased in AML patients compared with healthy controls [OR: 1.36, p=0.04; OR: 1.34, p=0.04; respectively]. However, rs1801157 demonstrated no significant differences in genotype distributions and allele frequency between AML patients and healthy controls. For the two combined SNPs, there was no significant proportional difference between the wild type GG-CC genotypes and non-GG-CC genotypes in AML patients and healthy controls. Additionally, peripheral blood leukemia-cell (PBLC) count was not statistically influenced by the genotypes of either rs1801157 or rs2228014. CONCLUSION: Genotype CT of rs2228014 appeared to correlate with AML risk, but played no role in leukemia cells invading the bloodstream, while rs1801157 and the two combined SNPs were not associated with either increased AML risk or extramedullary leukemia-cell dissemination.
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