Kaderi M A, Norberg M, Murray F, Merup M, Sundström C, Roos G, Aleskog A, Karlsson K, Axelsson T, Tobin G, Rosenquist R
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Leukemia. 2008 Feb;22(2):339-43. doi: 10.1038/sj.leu.2405042. Epub 2007 Nov 29.
The (-938C>A) polymorphism in the promoter region of the BCL-2 gene was recently associated with inferior time to treatment and overall survival in B-cell chronic lymphocytic leukemia (CLL) patients displaying the -938A/A genotype and may thus serve as an unfavorable genetic marker in CLL. Furthermore, the -938A/A genotype was associated with increased expression of Bcl-2. To investigate this further, we analyzed the -938 genotypes of the BCL-2 gene in 268 CLL patients and correlated data with treatment status, overall survival and known prognostic factors, for example, Binet stage, immunoglobulin heavy-chain variable (IGHV) mutational status and CD38 expression. In contrast to the recent report, the current cohort of CLL patients showed no differences either in time to treatment or overall survival in relation to usage of a particular genotype. In addition, no correlation was evident between the (-938C>A) genotypes and IGHV mutational status, Binet stage or CD38. Furthermore, the polymorphism did not appear to affect the Bcl-2 expression at the RNA level. Taken together, our data do not support the use of the (-938C>A) BCL-2 polymorphism as a prognostic marker in CLL and argue against its postulated role in modulating Bcl-2 levels.
BCL-2基因启动子区域的（-938C>A）多态性最近与B细胞慢性淋巴细胞白血病（CLL）患者较差的治疗时间和总生存期相关，这些患者表现出-938A/A基因型，因此可能是CLL中一个不利的遗传标志物。此外，-938A/A基因型与Bcl-2表达增加相关。为了进一步研究这一点，我们分析了268例CLL患者BCL-2基因的-938基因型，并将数据与治疗状态、总生存期以及已知的预后因素（如Binet分期、免疫球蛋白重链可变区（IGHV）突变状态和CD38表达）进行关联。与最近的报告相反，目前这组CLL患者在治疗时间或总生存期方面，无论使用何种特定基因型均无差异。此外，（-938C>A）基因型与IGHV突变状态、Binet分期或CD38之间均无明显相关性。此外，该多态性似乎并未在RNA水平上影响Bcl-2的表达。综上所述，我们的数据不支持将（-938C>A）BCL-2多态性用作CLL的预后标志物，并反对其在调节Bcl-2水平方面的假定作用。
