Altered expression of Bax protein has been shown to be predictive of overall and disease free-survival of patients with diffuse large B-cell lymphoma (DLCL)(

Am J Hematol, 2003; 73:101–7
). Further, absence of Bax and low levels of Bcl-2 have been shown to be associated with a more aggressive phenotype (P<0.05) (
Blood, 1997; 90:3173–8
) in patients with DLCL. We have previously reported a single nucleotide polymorphim (SNP), G125A, in the 5′-untranslated region of the BAX promoter and its association with reduced protein expression and treatment resistance in B-cell chronic lymphocytic leukemia (
Cancer Lett 2002; 187:199–205
). The aim of the present study was to evaluate BAX SNP incidence and its association with the protein expression in lymphomas. DNA was extracted from fifty lymphoma samples (31 DLCL, seven follicular lymphomas (FL), three marginal zone lymphomas (MZL), four T-cell lymphomas, three Hodgkin’s lymphomas, and two cases of Mantle cell lymphoma (MCL), and from 55 control samples. BAX SNP was detected by restriction enzyme analysis (
J Clin Pathol, 2003; 56: 205–9
). Fourteen out of 50 (28%) samples had G125A SNP, in all cases only one allele was replaced. It was present in eight (26%) DLCL, two (29%) FL, in two MZL, in one T-cell lymphoma, in one HL, and none of MCL had this SNP. Eight out of 55 (14.5%) controls had the SNP. The presence of BAX promoter SNP was associated with reduced Bax protein expression as detected by Western blot analysis (P=0.024). Two plasmids with G and A nucleotides at position 125 of the BAX promoter linked to luciferase as a reporter were constructed and used for transfection, as well as the pGL3-Basic and pGL3-Control plasmids; pRL-SV40 plasmid was used for co-transfection. Dual-Glo luciferase assay was performed and Firefly luciferase activity was normalized to Renilla luciferase. In transfection experiments, the G125A SNP reduced expression (P=0.0202) of BAX promoter. BAX SNP, G125A, present in approximately a quarter of DLCL has a direct negative effect on BAX gene expression.

Topics:
diffuse large b-cell lymphoma, gene expression, single nucleotide polymorphism, luciferases, lymphoma, bax protein, nucleotides, t-cell lymphoma, cancer, chronic b-cell leukemias

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2005, The American Society of Hematology
2005
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