Atypical lymphocytes in B-cell chronic lymphocytic leukemia and trisomy 12studied by conventional staining combined with fluorescence in situ hybridization

Trisomy 12 is one of the most frequent chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL), and is predominantly found in CLL with atypical morphology (aCLL). It has been suggested that the atypical morphol ogy might be a feature of the abnormal trisomy 12 clone, but so far it has been difficult to allocate chromosomal aberrations to individual leukemic c ells identified by cytomorphology. We therefore wanted to use our MGG/FISH method, which combines fluorescence in situ hybridization (FISH) and standa rd cytomorphology, to study, if the trisomy 12 clone in CLL was restricted to lymphocytes with atypical morphology. Peripheral blood specimens of four patients with aCLL were studied using a DNA probe against the pericentrome ric region of chromosome 12. Trisomy 12 was found in 10-34 % of the Lymphoc ytes. In three patients, the proportion of atypical and typical lymphocytes with trisomy 12 was quite comparable, and so was the percentage of atypica l cells with lymphoplasmacytoid morphology and those with cleaved nucleus s howing trisomy 12. Only one patient differed, since we found an overreprese ntation of trisomy 12 among the atypical lymphocytes. However, this could b e fully explained by the diluting effect of contaminating T-cells after che motherapy. The results of the present study show that despite the strong association o f trisomy 12 and atypical morphology in CLL, this chromosomal abnormality i s not confined to lymphocytes with atypical morphology: but is also found i n typical CLL cells. This supports that both cell types have the same clona l origin and that different cell morphology cannot be explained alone by th e acquisition elf an additional chromosome 12.