Coexistence of aneuploid subclones within a myeloma cell line that exhibits clonal immunoglobulin gene rearrangement : clinical implications

• Published in: Cancer research (Chicago, Ill.) Ill.), 1993-11, Vol.53 (21), p.5320-5327
• Main Authors: JELINEK, D. F, AHMANN, G. J, GREIPP, P. R, JALAL, S. M, WESTENDORF, J. J, KATZMANN, J. A, KYLE, R. A, LUST, J. A
• Format: Article
• Language: English
• Subjects: Aneuploidy; Antigens, CD - analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blotting, Southern; Cell Division - drug effects; Cell Line; Clone Cells; Culture Techniques - methods; Cytokines - pharmacology; DNA, Neoplasm - analysis; Female; Gene Rearrangement; Genes, Immunoglobulin; Genotype; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunophenotyping; Interleukin-6 - pharmacology; Karyotyping; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Phenotype; Recombinant Proteins - pharmacology; Restriction Mapping
• ISSN: 0008-5472; 1538-7445

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.