The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia

Abstract

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, V H mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n ¼ 207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and V H mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P ¼ 0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by V H mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.

Lack of association between the MDM2 promoter polymorphism SNP309 and clinical outcome in chronic lymphocytic leukemia

“…The presence of certain SNPs within the BAX [25], P2X7 [26], GNAS1 [27] and BCL2 [28] genes have been associated to disease progression and inferior survival for the patients. However, none of these potential SNPs have been confirmed in subsequent investigations by other groups [19,[29][30][31][32]. Thus, it is important that any potential SNP should be verified by large independent cohorts and independent research centers.…”

“…Genomic DNA was extracted from frozen tumor cells as previously described [19]. DNA was whole-genome amplified according to the manufacturer's protocol (GenomiPhi DNA Amplification, GE Healthcare, Uppsala, Sweden).…”

The role of certain gene polymorphisms involved in the apoptotic pathways in polycythemia vera and essential thrombocytosis

“…20 Skogsberg et al, however, concluded that the Bax-248 polymorphism had no role as a marker of survival and prognosis in CLL. 21 The exact cause of MPNs is unknown. However, molecular-genetic studies suggest that the majority of this type of neoplasm may be the result of acquired clonal genetic events.…”

The BCL-2 promoter (−938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia

“…11 DNA was whole-genome amplified according to the manufacturer's protocol (GenomiPhi DNA Amplification, GE Healthcare, Uppsala, Sweden). For genotyping, information on PCR and minisequencing primers was collected from the SNP assay database (http://las.perkinelmer.com/content/forms/SNPDatabase/ welcome.asp).…”

“…9 Recently, single-nucleotide polymorphisms (SNPs) within certain genes (BAX, P2X7, GNAS1 and MCL-1) have also been associated with disease progression and clinical outcome, although none of these studies has been confirmed in subsequent studies from other centers. [10][11][12][13][14][15][16][17] Bcl-2 belongs to a growing family of apoptosis-regulatory gene products, comprising both proapoptotic (Bax, Bak, Bcl-X S , Bad, Bid, Bik and Hrk) and antiapoptotic (Bcl-2, Bcl-X L , Bcl-W, Brag-1, Mcl-1 and Bfl-1/A1) members. 18,19 CLL cells have been shown to display dysregulated apoptosis with high expression of the Bcl-2 protein in most cases.…”