Takishita M, Kosaka M, Goto T, Saito S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Br J Haematol. 1994 Aug;87(4):735-42. doi: 10.1111/j.1365-2141.1994.tb06732.x.
The cellular origin and extent of clonal involvement in multiple myeloma (MM) are controversial. The third-complementarity-determining region (CDR3) of the immunoglobulin heavy chain gene is the target region of VH replacements and somatic mutations. We analysed the CDR3 sequences of myeloma cells from eight newly diagnosed and three relapsed patients in order to elucidate the target cell of malignant transformation in MM. We also examined the extent of clonal involvement in MM using a CDR3 clone-specific nucleic acid probe. The peripheral lymphocytes from the five MM patients were separated into fractions such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- and CD2+ cells. Amplified CDR3 DNAs from these subpopulations were hybridized with the probe specific to each patient's tumour cells. We found no evidence of ongoing VH replacements or somatic mutations in CDR3 in MM. However, frequent nucleotide mutations in D and JH segments were observed. Circulating malignant cells were detected in the CD34+ and all of the CD20+ subpopulations, but not in the CD2+ fraction. MM is a neoplasm originating from a B-lineage cell which has already undergone antigen-dependent selection. Nevertheless, the tumour cells are composed of heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. Conversely, T cells were not involved in MM. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM.
多发性骨髓瘤（MM）中克隆性累及的细胞起源及范围存在争议。免疫球蛋白重链基因的第三互补决定区（CDR3）是VH替换和体细胞突变的靶区域。我们分析了8例新诊断和3例复发患者骨髓瘤细胞的CDR3序列，以阐明MM恶性转化的靶细胞。我们还使用CDR3克隆特异性核酸探针检测了MM中克隆性累及的范围。将5例MM患者的外周淋巴细胞分离为CD34 +、CD20 + CD10 +、CD20 + CD21 +、CD20 + CD19 -和CD2 +细胞等组分。来自这些亚群的扩增CDR3 DNA与针对每位患者肿瘤细胞的探针杂交。我们未发现MM中CDR3存在持续的VH替换或体细胞突变的证据。然而，在D和JH片段中观察到频繁的核苷酸突变。在CD34 +和所有CD20 +亚群中检测到循环恶性细胞，但在CD2 +组分中未检测到。MM是一种起源于已经历抗原依赖性选择的B谱系细胞的肿瘤。然而，肿瘤细胞由处于不同分化阶段的异质性亚群组成，类似于正常B谱系细胞。相反，T细胞未参与MM。这些结果表明正常B谱系细胞与MM肿瘤细胞之间存在类似的发育途径。
