Longitudinal analysis of circulating myeloma cells detected by allele specific mRNA in situ hybridization.

Individual myeloma cells in the peripheral blood of 7 patients with multiple myeloma were detected by mRNA in situ hybridization (ISH) using biotinylated antisense oligonucleotide probes to non-germline sequences of the CDR3 region of the immunoglobulin heavy chain gene. Peripheral blood samples from these patients were studied over a period of 2-3 years. The number of circulating myeloma cells varied from 0.1-23% of the mononuclear cell population. Longitudinal studies showed that the highest number of circulating myeloma cells were present during escape phase and thus the percentage of mRNA ISH+ cells correlated with the clinical state of the patient. This technique is the most accurate means of monitoring and quantitating individual myeloma cells in the peripheral blood of patients with myeloma and provides insight into the relevance of circulating myeloma cells.