SEVERAL CYTOGENETIC SUBCLONES MAY BE IDENTIFIED WITHIN PLASMA-CELLS FROM PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE, BOTH AT DIAGNOSIS AND DURING THE INDOLENT COURSE OF THIS CONDITION

Monoclonal gammopathy of undetermined significance (MGUS) is a frequen t condition in patients over 50 years old, that ultimately leads to mu ltiple myeloma (MM) in 20% of patients after 20 to 35 years of follow- up, little is known about cytogenetic changes associated with this con dition. We studied 19 MGUS patients both at diagnosis and after 12 to 35 months of follow-up (mean = 26), using DNA content measurement of h one marrow plasma cells (BMPC), and a new interphase fluorescence in s itu hybridization technique (FISH) allowing the simultaneous identific ation of monotypic BMPC (fluorescent anti light-chain antibodies) and the determination of the number of copies for two different chromosome s within the same PC nucleus (one biotin-labeled probe coupled next to texas red avidin and one FITC labeled probe). At diagnosis of the MGU S, single interphase FISH showed at least one numeric chromosome chang e in 13 of 19 patients, after the use of centromeric probes directed a gainst chromosomes no, 3, no. 7, no, 9, and no, 11. At follow-up, abno rmalities found at diagnosis in 13 patients were still shown. Moreover , abnormalities occurred in three of the last six patients (trisomy fo r one to three different chromosomes), although no patient evolved int o MM. Dual interphase FISH showed that some BMPC bore numeric changes with both probes tested whereas other BMPC bore abnormality with only one of the probes tested. In patients who showed trisomy for at least three different chromosomes, distribution of numeric changes within BM PC defined significant numbers of up to seven different BMPC clones. A ll these various clones were shown both at diagnosis and at follow-up. In every patient, these various clones differed only for the number o f abnormalities they exhibited, and could be related to each other in a model of gradual acquisition of chromosome changes. Eventually, data reported here show that MGUS patients acquire slowly, gradually, but ineluctably chromosome changes, distributed within several related sub clones, However, these changes are not related to transformation into MM: among the various clones coexisting within the same patient, a pec uliar change, still to demonstrate, might develop and lead to overt MM . (C) 1997 by The American Society of Hematology.