Association of a novel regulatory polymorphism (−938C>A) in the BCL2 gene promoter with disease progression and survival in chronic lymphocytic leukemia

Abstract

Bcl-2 plays a key role in the regulation of apoptosis. We investigated the role of a novel regulatory single-nucleotide polymorphism (؊938C>A) in the inhibitory P2 BCL2 promoter in B-cell chronic lymphocytic leukemia (B-CLL

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

“…Also contrary to the study by Nuckel et al, 26 we did not find any significant difference in the length of the progression-free interval as indicated by time from diagnosis to the first treatment in our CLL cohort. Moreover, there was no indication that the BCL-2 polymorphism affects disease progression in CLL patients within any specific Binet stage or within mutated/unmutated subgroups.…”

“…It should be noted that our study cohort consists of a higher proportion of Binet stage B and C cases and cases carrying unmutated IGHV rearrangements. Thus, our cohort seems to have more aggressive clinical course than in the study by Nuckel et al 26 That notwithstanding, similar findings were observed when only stage A and mutated cases were analyzed. Furthermore, when the BCL-2 genotype status was combined with IGHV mutation data, no significant difference in overall survival was evident within either the IGHV-mutated or unmutated subgroups.…”

“…This polymorphism was found on the second promoter, P2, of the BCL-2 gene, which was characterized as a negative modulator of the first promoter, P1, and subsequently, BCL-2 gene expression. 25 A recent work by Nuckel et al 26 reported that the presence of the À938A/A genotype was associated with decreased activity of the P2 and increased Bcl-2 protein expression in CLL. These authors also suggested the BCL-2 (À938C4A) polymorphism as a novel prognostic marker in CLL, since they reported a significantly worse median overall survival and progressive-free survival in CLL patients carrying the A/A genotype as compared to patients with C þ alleles.…”

“…26 Of the 268 CLL samples investigated, 122 (46%) displayed a heterozygous genotype for the BCL-2 (À938C4A) polymorphism, while 89 (33%) and 57 (21%) of the patients were homozygous for the A/A and C/C genotype, respectively. There was no difference in median age of diagnosis between the three groups; 63, 65 and 67 years in patients with À938A/A, À938A/C and À938C/C genotypes, respectively.…”

“…25 Recently, an SNP (À938C4A) in the P2 position of BCL-2 gene was reported to serve as a predictor for disease progression and overall survival in CLL. 26 The investigators showed that CLL patients with the À938A/A genotype had shorter median overall survival and median time from first diagnosis to initiation of chemotherapy compared with those with À938AC/CC genotypes. The À938A/A genotype was also indicated as an independent prognostic factor for progression-free survival in CLL.…”