Jelinek D F, Ahmann G J, Greipp P R, Jalal S M, Westendorf J J, Katzmann J A, Kyle R A, Lust J A
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Cancer Res. 1993 Nov 1;53(21):5320-7.
A new human myeloma cell line, ANBL-6, was established and characterized at the genotypic and phenotypic levels. The cells exhibit a clonally rearranged immunoglobulin gene locus and resemble plasma cells morphologically. The ANBL-6 cells also exhibited an absolute dependence on exogenous interleukin 6 for growth. Of interest, DNA ploidy analysis suggested the existence of a near-diploid as well as a near-tetraploid population in this cell line. Cytogenetic studies confirmed the existence of two aneuploid karyotypes and further revealed a clonal relationship between the two karyotypes, as evidenced by numerous shared structural abnormalities. To determine whether the near-diploid cells functioned as stem cells for the near-tetraploid population, the near-diploid population was separated via flow cytometry and recultured prior to ploidy analysis. This population was observed to remain predominantly near-diploid over time, suggesting that these cells did not function as stem cells for the near-tetraploid population. However, the near-tetraploid cells did exhibit a growth advantage in vitro. Moreover, sequential ploidy analysis performed retrospectively on fresh bone marrow cells from the patient also suggested that there was an expansion of the near-tetraploid population during clinical relapse. These results suggest that both populations are self-regenerating and reflect the consequences of clonal evolution in the myeloma tumor. The coexistence of clonally related subclones with shared chromosomal abnormalities, however, suggests that the near-tetraploid subclone was derived from the near-diploid subclone at an unknown time during tumorigenesis.
建立了一种新的人骨髓瘤细胞系ANBL - 6，并在基因型和表型水平对其进行了表征。这些细胞表现出克隆重排的免疫球蛋白基因座，并且在形态上类似于浆细胞。ANBL - 6细胞在生长方面还表现出对外源性白细胞介素6的绝对依赖性。有趣的是，DNA倍性分析表明该细胞系中存在近二倍体以及近四倍体群体。细胞遗传学研究证实了两种非整倍体核型的存在，并进一步揭示了两种核型之间的克隆关系，大量共享的结构异常证明了这一点。为了确定近二倍体细胞是否作为近四倍体群体的干细胞发挥作用，通过流式细胞术分离近二倍体群体，并在进行倍性分析之前进行再培养。观察到该群体随着时间的推移主要保持近二倍体状态，这表明这些细胞不作为近四倍体群体的干细胞发挥作用。然而，近四倍体细胞在体外确实表现出生长优势。此外，对患者新鲜骨髓细胞进行的回顾性连续倍性分析还表明，在临床复发期间近四倍体群体有所扩增。这些结果表明这两个群体都是自我更新的，反映了骨髓瘤肿瘤中克隆进化的结果。然而，具有共享染色体异常的克隆相关亚克隆的共存表明，近四倍体亚克隆在肿瘤发生过程中的某个未知时间源自近二倍体亚克隆。
