Jarosova Marie, Kriegova Eva, Schneiderova Petra, Fillerova Regina, Prochazka Vit, Mikesova Michaela, Flodr Patrik, Indrak Karel, Papajik Tomas
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
Pathol Oncol Res. 2016 Apr;22(2):233-43. doi: 10.1007/s12253-015-9972-1. Epub 2015 Aug 30.
BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the "major breakpoint region" encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with "alternative breakpoint cluster" located 245-285 kb 5' BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5' untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5' untranslated region of BCL6 and 5' untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era.
BCL6重排（3q27）是弥漫性大B细胞淋巴瘤（DLBCL）中最常见的染色体异常，有众多免疫球蛋白（Ig）和非Ig基因作为伙伴基因。在DLBCL中，易位主要发生在包含BCL6第一个非编码外显子和第一个内含子一部分的“主要断裂点区域”；也有少数病例的“替代断裂点簇”位于BCL6 5'端245 - 285 kb处。已知Ig和非Ig伙伴基因的调控序列以相同转录方向取代了BCL6的5'非翻译区。与高BCL6基因表达典型的Ig/BCL6融合相反，在非Ig/BCL6易位中观察到BCL6 mRNA水平意外地低。从临床角度看，具有非Ig伙伴基因的DLBCL患者的生存率低于具有Ig/BCL6易位的患者，这表明非Ig/BCL6融合是一个不良预后指标。在此，我们提供了关于DLBCL中已知非Ig易位伙伴基因以及BCL6重排临床后果的全面信息。此外，我们描述了一例难治性DLBCL患者中的一种新的相互易位t(3;10)，断裂点位于10号染色体q11.21位点上BCL6的5'非翻译区和RASGEF1A基因的5'非翻译区；这种重排与低BCL6和RASGEF1A基因表达相关。我们的患者存在涉及BCL2和BCL6基因的双重染色体重排，复发三次并很快死亡；因此，进一步支持了非Ig/BCL6融合是DLBCL不良预后指标的观点。在利妥昔单抗时代，也有证据表明BCL6重排具有预后价值。
