TRISOMY-12 IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA - ASSESSMENT OF LINEAGE RESTRICTION BY SIMULTANEOUS ANALYSIS OF IMMUNOPHENOTYPE AND GENOTYPE IN INTERPHASE CELLS BY FLUORESCENCE IN-SITU HYBRIDIZATION

We have studied the lineage restriction of trisomy 12 in six patients with B-cell chronic lymphocytic leukaemia (CLL) by simultaneous analys is of immunophenotype and fluorescence in situ hybridization (FISH) si gnals in single interphase cells. Fresh uncultured cells from each pat ient were immunophenotyped by the alkaline phosphatase antialkaline ph osphatase method (APAAP) using monoclonal or polyclonal antibodies and hybridized with a chromosome 12 specific alpha-satellite DNA probe. I n all cases trisomy 12 was restricted to the clonal B-cells, kappa pos itive or lambda positive, whereas T-cells (CD3 positive) and non clona l B-cells had only two chromosome 12 signals. Within the clonal B-cell population a large proportion of cells were disomic for chromosome 12 , whilst trisomic cells ranged from 21% to 37%. The absence of trisomy 12 in T-cells and the mosaicism demonstrated in the clonal B-cells su ggests that this abnormality is a secondary event during the leukaemic transformation of CLL and develops in an already established neoplast ic B-cell population.