Dyer M J, Zani V J, Lu W Z, O'Byrne A, Mould S, Chapman R, Heward J M, Kayano H, Jadayel D, Matutes E
Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Sutton, Surrey, UK.
Blood. 1994 Jun 15;83(12):3682-8.
Although translocations of the BCL2 gene are frequent in B-cell non-Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B-cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B-CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI-HindIII fragment indicating a clustering of breakpoints. Two cases of B-CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms.
尽管BCL2基因易位在B细胞非霍奇金淋巴瘤（B-NHL）中很常见，但在表型相关的成熟B细胞慢性白血病中，类似易位的发生率、性质和预后意义尚不清楚。因此，我们使用5'和3' BCL2探针，通过DNA印迹法检测了170例B细胞慢性淋巴细胞白血病（B-CLL）、7例B细胞幼淋巴细胞白血病（B-PLL）、25例毛细胞白血病（HCL）和22例伴有绒毛状淋巴细胞的脾淋巴瘤（SLVL），这些病例均有明确的细胞遗传学异常，以寻找BCL2基因座的重排。在3例B-CLL中通过细胞遗传学检测到易位t(14;18) (q32.3;q21.3)。所有病例的BCL2 3'区域均有断点，定位于主要断点区域（MBR）和次要簇区域（mcr）之间，这是在B-NHL中常见检测到的断点簇。在这3例中的2例中，BCL2内的断点定位于一个1.0-kb的EcoRI-HindIII片段，表明断点成簇。2例B-CLL通过细胞遗传学检测到t(2;18)(p11;q21.3)或t(18;22)(q21.3;q11)。两者均将BCL2基因的5'区域重排至相应的免疫球蛋白轻链基因。t(18;22)(q21.3;q11)的分子克隆显示，该易位破坏了BCL2启动子区域和BCL2第一个非翻译外显子。然而，在该病例中仍可见高水平的BCL2蛋白。仅另外2例细胞遗传学分析未成功的病例显示BCL2 5'区域重排，总体发生率为2.3%。B-PLL、HCL或SLVL病例均未显示5'或3' BCL2重排。这些数据证实了细胞遗传学观察结果，即所有形式的成熟B细胞白血病中涉及BCL2基因座的易位很少见，且仅限于B-CLL的一小部分。B-CLL中的BCL2易位涉及BCL2基因5'和3'区域的重组热点，这与B-NHL中常见的热点不同，提示有不同的致病机制。
