Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11010 Belgrade, Serbia.
Med Oncol. 2013 Mar;30(1):405. doi: 10.1007/s12032-012-0405-7. Epub 2013 Jan 5.
Dysregulation of apoptosis is a distinctive feature of chronic lymphocytic leukemia (CLL), although a unique mechanism underlying apoptosis resistance of CLL B lymphocytes has not been identified yet. Aberrant expression as well as genetic and epigenetic alterations of numerous genes involved in different pathways of apoptosis regulation has been described in CLL. Here, we report the expression analysis of Bcl2L12 (Bcl2-like 12), a novel apoptotic gene belonging to Bcl2 family, in 58 Serbian CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2L12 mRNA in CLL samples compared to non-leukemic samples, implying its role in the pathogenesis of the disease. Receiver operating characteristic (ROC) analysis showed that Bcl2L12 expression efficiently discriminates CLL cases from healthy controls. However, relatively homogenous Bcl2L12 mRNA expression among patients did not reflect their clinical characteristics (with the exception of lactate dehydrogenase status and time from diagnosis to treatment) and failed to show association with the most informative prognostic markers, namely the mutational status of rearranged immunoglobulin heavy chain variable region genes, CD38 and lipoprotein lipase gene (LPL) expression.
细胞凋亡失调是慢性淋巴细胞白血病(CLL)的一个显著特征,尽管尚未确定导致 CLL B 淋巴细胞凋亡抵抗的独特机制。在 CLL 中已经描述了许多参与细胞凋亡调控不同途径的基因的异常表达以及遗传和表观遗传改变。在这里,我们报告了属于 Bcl2 家族的新型凋亡基因 Bcl2L12(Bcl2 样 12)在 58 名塞尔维亚 CLL 患者中的表达分析。定量逆转录聚合酶链反应(qRT-PCR)分析显示,与非白血病样本相比,CLL 样本中 Bcl2L12 mRNA 的表达显著上调,提示其在疾病发病机制中的作用。接收器操作特征(ROC)分析表明,Bcl2L12 表达能够有效地将 CLL 病例与健康对照区分开来。然而,患者之间相对均匀的 Bcl2L12 mRNA 表达并不能反映其临床特征(除了乳酸脱氢酶状态和从诊断到治疗的时间),并且未能显示与最具信息性的预后标志物相关,即重排免疫球蛋白重链可变区基因、CD38 和脂蛋白脂肪酶基因(LPL)表达的突变状态。