Ploidy, as Detected by Fluorescence In Situ Hybridization, Defines Different Subgroups in Multiple Myeloma.

Ploidy appears as an important parameter in both the biology and the clinical evolution of multiple myeloma. However, its evaluation requires either a successful karyotyping (obtained in 30% of the patients), or a DNA index calculation by flow cytometry (not routinely performed in myeloma). We validated a novel method for the detection of hyperdiploidy based on interphase fluorescence in situ hybridization (FISH) that can be utilized on almost all patients. We selected a 3-color probe set composed of probes specific for chromosomes 5, 9, and 15. Two hundred and five patients with myeloma were analyzed by flow cytometry (DNA Index) and FISH, and results obtained by both techniques were then compared. As shown in the table, FISH was very specific and sensitive for the detection of hyperdiploidy. Only 6 of the 104 hyperdiploid patients, all with a low hyperdiploidy (DNA Index <1.10), were classified as diploid by FISH. Extended studies looking for t(4;14), t(11;14), and del(13q14) showed that most recurrent 14q32 translocations occur in non-hyperdiploid clones, and that deletions of chromosome 13 were less frequently observed in hyperdiploid clones (48% vs 66%). These data confirmed that chromosomal abnormalities are not randomly distributed in myeloma and that FISH allows analysis of all the major chromosomal abnormalities. Further large studies are ongoing to evaluate the prognostic value of ploidy in myeloma and to correlate the true prognostic value of all chromosomal abnormalities.