Jantus Lewintre Eloisa, Reinoso Martín Cristina, García Ballesteros Carlos, Pendas Jehzabel, Benet Campos Carmen, Mayans Ferrer José Ramón, García-Conde Javier
Molecular Haematology Laboratory, Prince Felipe Research Centre, Valencia, Spain.
Leuk Lymphoma. 2009 May;50(5):773-80. doi: 10.1080/10428190902842626.
BCL6 somatic mutations affect normal and tumoral post germinal center B-lymphocytes. Our objective was to analyse expression, mutations and polymorphisms in the BCL6 gene and to correlate those variables with the clinical outcome in early-stage chronic lymphocytic leukemia (CLL). CLL samples were used for characterisation of the mutational status of BCL6/ immunoglobulin variable heavy chain (IGHV) genes, and expression of BCL6 was determined by real time PCR and immunoblot. Out of 68 cases, 29% show somatic mutations on BCL6 which occur exclusively in IGHV mutated cases. They are single nucleotide substitutions located mainly in two short mutational hot spots. CLL cells express different levels of BCL6 regardless of the mutational status, the number of mutations and polymorphisms. CLL cases expressing high levels of BCL6 have significantly shorter treatment-free interval. In conclusion, in early-stage patients with CLL, we found no correlation between expression and the mutations or polymorphism in BCL6, but high levels of BCL6 can discriminate patients with a worse prognosis.
BCL6体细胞突变影响生发中心后正常和肿瘤性B淋巴细胞。我们的目的是分析BCL6基因的表达、突变和多态性，并将这些变量与早期慢性淋巴细胞白血病（CLL）的临床结局相关联。使用CLL样本对BCL6/免疫球蛋白重链可变区（IGHV）基因的突变状态进行表征，并通过实时PCR和免疫印迹法测定BCL6的表达。在68例病例中，29%表现出BCL6体细胞突变，这些突变仅发生在IGHV突变的病例中。它们是主要位于两个短突变热点的单核苷酸替换。无论突变状态、突变数量和多态性如何，CLL细胞均表达不同水平的BCL6。表达高水平BCL6的CLL病例的无治疗间隔明显更短。总之，在早期CLL患者中，我们发现BCL6的表达与突变或多态性之间无相关性，但高水平的BCL6可区分预后较差的患者。
