Cherepakhin V, Baird S M, Meisenholder G W, Kipps T J
Department of Medicine-0663, University of California at San Diego, La Jolla 92093-0663.
Blood. 1993 Nov 15;82(10):3141-7.
Patients with B-cell chronic lymphocytic leukemia (CLL) infrequently may develop high-grade B-cell lymphoma, or Richter's syndrome lymphoma (RS lymphoma). Such lymphomas differ from the original leukemia in both histology and clinical behavior. Studies seeking to define the clonal relationship between the cells of the two malignancies in any one patient have yielded conflicting reports. We examined the clonal relationship between the early and late neoplastic cells of a patient who underwent Richter's transformation. In contrast to the original leukemia cells, the secondary high-grade lymphoma was CD5-. However, both the leukemia cells and the evolved RS lymphoma expressed surface IgM lambda reactive with Lc1, a murine monoclonal antibody specific for a supratypic cross-reactive idiotype encoded by a subset of human Ig variable region genes of the VH4 subgroup. Nucleic acid sequence analyses of the heavy and light chain variable region genes expressed by both leukemia and lymphoma cells show that the CD5- B-cell lymphoma constitutes a clonal expansion of mutant cells derived from the original CD5+ B-cell leukemia. Moreover, certain sets of somatic mutations distinguish the Ig variable region genes used by RS lymphoma from those expressed by the CLL B cells. This is the first study to establish the clonal relationship between CLL and RS lymphoma through primary structural analyses of the expressed Ig genes.
B细胞慢性淋巴细胞白血病（CLL）患者偶尔会发展为高级别B细胞淋巴瘤，即里氏综合征淋巴瘤（RS淋巴瘤）。此类淋巴瘤在组织学和临床行为上均与原始白血病不同。旨在确定任一患者两种恶性肿瘤细胞之间克隆关系的研究得出了相互矛盾的报告。我们研究了一名发生里氏转化患者早期和晚期肿瘤细胞之间的克隆关系。与原始白血病细胞不同，继发性高级别淋巴瘤CD5阴性。然而，白血病细胞和演变而来的RS淋巴瘤均表达与Lc1反应的表面IgM λ，Lc1是一种针对由VH4亚组的人类Ig可变区基因子集编码的超型交叉反应独特型的鼠单克隆抗体。对白血病细胞和淋巴瘤细胞表达的重链和轻链可变区基因进行的核酸序列分析表明，CD5阴性B细胞淋巴瘤是源自原始CD5阳性B细胞白血病的突变细胞的克隆扩增。此外，某些体细胞突变集区分了RS淋巴瘤使用的Ig可变区基因与CLL B细胞表达的基因。这是第一项通过对表达的Ig基因进行一级结构分析来确定CLL与RS淋巴瘤之间克隆关系的研究。
