The proliferation of multiple myeloma colonies (MY-CFUc) in vitro is independent of prognosis and is not associated with mutated N- or K-ras alleles in human bone marrow aspirates.
During the period September 1987 to March 1993 the proliferation of myeloma cells as colonies (MY-CFUc) in vitro was examined in bone marrow aspirates from 43 patients with multiple myeloma and two patients with Waldenström's macroglobulinaemia. Twenty-four samples from 45 patients, of whom three were at presentation, four were in complete remission (CR), six had achieved a partial response (PR) and 11 had progressive disease (PD), produced MY-CFUc in vitro. The same bone marrow aspirates or one taken within 2 months of that assessed for MY-CFUc were used in the polymerase chain reaction (PCR). Genomic DNA was analysed for mutations in N- and K-ras by slot blotting of the amplified products from the PCR with 32P-labelled probes and by direct sequencing. No mutations were detected in N- or K-ras proto-oncogenes at codons 12, 13 or 61 in any sample. Eleven of the patients from whom MY-CFUc were produced remain alive with a median survival of 73 months (range 15-75 months). MY-CFUc have been cultured from 19 of these 24 patients on subsequent occasions, of whom nine remain alive. Among patients whose cells did not produce MY-CFUc in vitro at the time of sampling for mutated ras alleles, biopsy samples from four patients have produced MY-CFUc in vitro on subsequent occasions, of whom one patient remains alive. The data show that the proliferation of MY-CFUc in vitro occurred independently of disease status and was not indicative of prognosis. The failure to detect mutated N- or K-ras alleles in any sample suggests that if such mutations were present in the cells which form colonies in vitro they represented less than 0.1% of the tumour burden and did not affect the survival of this group of patients.
Section of Academic Haematology, McElwain Laboratories, Institute of Cancer Research, Sutton, Surrey, UK.
B C
BC
Millar
J B
JB
Bell
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R
Barfoot
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M
Everard
D000483:Alleles; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm