INTERPHASE FLUORESCENCE IN-SITU HYBRIDIZATION IDENTIFIES CHROMOSOMAL-ABNORMALITIES IN PLASMA-CELLS FROM PATIENTS WITH MONOCLONAL GAMMOPATHYOF UNDETERMINED SIGNIFICANCE

Karyotypic studies in patients with monoclonal gammopathy of undetermi ned significance (MGUS) have been hampered by a low percentage of bone marrow plasma cells (BMPC), which are predominantly nonproliferating. By combining cytomorphology and interphase fluorescence in situ hybri dization (FISH) we investigated whether or not chromosomal abnormaliti es occur in BMPC from patients with MGUS. Studying chromosomes 3, 7, 1 1, and 18, which we found to be frequently aneuploid by FISH in multip le myeloma (MM), we observed three hybridization signals for one of th ese chromosomes in 19 of 36 patients (52.8%), Gains of chromosome 3 we re most common, occurring in 38.9% of patients, followed by gains of c hromosomes 11 (25%), 7 (16.7%), and 18 (5.6%). Among BMPC, the frequen cy of aneuploid cells was 18.9% +/- 13.9% (mean +/- SD) for chromosome 3, 22.3% +/- 9.2% for chromosome 11, 23.2% +/- 22.0% for chromosome 7 , and 6.1% +/- 2.3% for chromosome 18. In five patients, chromosomal a bnormalities were shown to be restricted to BMPC expressing cytoplasmi c immunoglobulins corresponding to the serum paraprotein. No gain of h ybridization signals was observed in normal and reactive plasma cells. In one patient with MGUS, metaphase cytogenetics revealed one abnorma l metaphase with 47,XY,+4, and trisomy 4 was also demonstrated in a su bpopulation of BMPC by interphase FISH. FISH results from patients wit h MGUS and newly diagnosed MM at stage IA (n = 14) indicated that aber rations involving greater than or equal to 2 chromosomes occurred sign ificantly more often in early stage MM (P < .01), With respect to clin ical and laboratory features, MGUS patients with and without chromosom al abnormalities were indistinguishable. Our results indicate that MGU S already has the chromosomal characteristics of a plasma cell maligna ncy. (C) 1995 by The American Society of Hematology.