Coexistence of aneuploid subclones within a myeloma cell line that exhibits clonal immunoglobulin gene rearrangement: clinical implications.
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.
Jelinek
D F
DF
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Ahmann
G J
GJ
Greipp
P R
PR
Jalal
S M
SM
Westendorf
J J
JJ
Katzmann
J A
JA
Kyle
R A
RA
Lust
J A
JA
D000782:Aneuploidy; D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D046508:Culture Techniques / Q000379:methods; D016207:Cytokines / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology; D007621:Karyotyping; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping
D015703:Antigens, CD; D016207:Cytokines; D004273:DNA, Neoplasm; D015850:Interleukin-6; D011994:Recombinant Proteins