SINGLE-CELL TRISOMY IN HEMATOLOGIC MALIGNANCY - RANDOM CHANGE OR TIP OF THE ICEBERG

Finding a clone in the bone marrow of a patient with a hematologic dis order is important to confirm the neoplastic nature of the disease and may be indicative of prognosis. Since cytogenetic analysis detects on ly actively dividing clones, the presence of a single abnormal cell am ong 20 cells analyzed raises doubts about its clonal nature. Fluoresce nce in situ hybridization (FISH) enables rapid detection of certain ch romosomal abnormalities in metaphase and interphase cells, thus enabli ng detection of minor or inactive clones; Seven patients with hematolo gic malignancy each having random cell (s) were investigated thus: at diagnosis, with MDS and a cell with +8 (two cases) or +9 (one case) an d with AML and a cell with +4 (one case), +7 (one case), or two cells with +9, +22/+10, +17 +17 (one case). One patient with ALL in remissio n had one cell with trisomy 4. One patient, a male aged 66 years with refractory anemia with ringed sideroblasts, was found to have a minor trisomy 8 clone in his diagnostic marrow. A follow-up marrow 42 months later showed no trisomy 8 cell among 62 metaphases analyzed, and the percentage of trisomic cells using FISH on interphase cells was within the control range. This patient has survived for more than 42 months requiring no treatment. Single-cell abnormalities in the other six cas es proved to be random events. Thus it appears that single-cell abnorm alities may not be clonal or at most indicate the presence of a minor clone well below the level of cytogenetic detection. The prognostic si gnificance of such minor clones is at present unclear.