Nakamura Y
Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan.
Leuk Lymphoma. 2000 Aug;38(5-6):505-12. doi: 10.3109/10428190009059269.
The BCL6 gene, encoding a POZ/Zinc finger protein which acts as a transcriptional repressor, is frequently altered at its 5' non-coding region by 3q27 chromosomal translocations in B-cell non-Hodgkin's lymphoma (NHL). BCL6 rearrangement is one of the most common genetic abnormalities in NHL. As a result of translocations, the regulatory region of the BCL6 gene is replaced by an heterologous reciprocal partner such as the immunoglobulin (IG) genes. Promotor substitution leads to deregulation of the BCL6 expression, which may be associated with lymphomagenesis. Recent studies have shown that the 5' non-coding region of the BCL6 gene is also subject to somatic hypermutation physiologically operating in germinal center (GC) B-cells in a similar pattern to that of the IG genes. There is little evidence to show that structural alterations of the BCL6 gene may be caused by mechanisms other than chromosomal translocations. To date, five cases with NHL exhibiting gross BCL6 deletions of the 1.5-2.4 kb have been reported. These deletions occurred in the same region as translocational breakpoints and the somatic hypermutations cluster, but independently of chromosomal rearrangements. The deletions overlapped at the 270 bp region and this region contains a putative protein-binding sequence which may play a role in the regulation of the BCL6 expression. Small separated deletions of 22-101 bp, which may also contain protein-binding sequences, were evident in another NHL case. In contrast to the TAL1 deletion in T-cell acute lymphoblastic leukemia (ALL), the BCL6 deletion is considered to be mediated by a mechanism other than aberrant activity of the IG recombinase. Internal deletion within the BCL6 gene is a recurrent molecular abnormality in B-cell NHL, which is sometimes indistinguishable from rearrangements by chromosomal translocations. At present, the mechanism of DNA recombination and its role in lymphomagenesis remain unknown.
BCL6基因编码一种作为转录抑制因子的POZ/锌指蛋白，在B细胞非霍奇金淋巴瘤（NHL）中，其5'非编码区常因3q27染色体易位而发生改变。BCL6重排是NHL中最常见的基因异常之一。由于易位，BCL6基因的调控区被一个异源的相互作用伙伴如免疫球蛋白（IG）基因所取代。启动子替代导致BCL6表达失调，这可能与淋巴瘤发生有关。最近的研究表明，BCL6基因的5'非编码区在生发中心（GC）B细胞中也会发生体细胞超突变，其生理作用模式与IG基因相似。几乎没有证据表明BCL6基因的结构改变可能由染色体易位以外的机制引起。迄今为止，已报道了5例NHL病例，其BCL6基因出现了1.5 - 2.4 kb的大片段缺失。这些缺失发生在与易位断点和体细胞超突变簇相同的区域，但与染色体重排无关。这些缺失在270 bp区域重叠，该区域包含一个可能在BCL6表达调控中起作用的假定蛋白结合序列。在另一例NHL病例中，还发现了22 - 101 bp的小片段分离缺失，这些缺失也可能包含蛋白结合序列。与T细胞急性淋巴细胞白血病（ALL）中的TAL1缺失不同，BCL6缺失被认为是由IG重组酶异常活性以外的机制介导的。BCL6基因内部缺失是B细胞NHL中一种反复出现的分子异常，有时与染色体易位导致的重排难以区分。目前，DNA重组机制及其在淋巴瘤发生中的作用仍不清楚。
