Coexistence of aneuploid subclones within a myeloma cell line that exhibits clonal immunoglobulin gene rearrangement: clinical implications
| Autor: | D F, Jelinek, G J, Ahmann, P R, Greipp, S M, Jalal, J J, Westendorf, J A, Katzmann, R A, Kyle, J A, Lust |
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| Rok vydání: | 1993 |
| Předmět: |
Gene Rearrangement
Genes Immunoglobulin Genotype Interleukin-6 Restriction Mapping DNA Neoplasm Middle Aged Aneuploidy Recombinant Proteins Cell Line Clone Cells Immunophenotyping Blotting Southern Phenotype Antigens CD Culture Techniques Karyotyping Antineoplastic Combined Chemotherapy Protocols Cytokines Humans Female Multiple Myeloma Cell Division |
| Zdroj: | Cancer research. 53(21) |
| ISSN: | 0008-5472 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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