TRISOMY-12 AND P53 DELETION IN CHRONIC LYMPHOCYTIC-LEUKEMIA DETECTED BY FLUORESCENCE IN-SITU HYBRIDIZATION - ASSOCIATION WITH MORPHOLOGY AND RESISTANCE TO CONVENTIONAL CHEMOTHERAPY

The incidence of trisomy 12 and p53 deletion was studied in a group of chronic B-lymphocytic leukemia (B-CLL) patients, using fluorescence i n situ hybridization (FISH). Trisomy 12 was defected in eight of 50 pa tients (16%) and p53 deletion in six of 38 cases analyzed (15.8%). A s tatistically significant difference was observed between the incidence of trisomy 12 in patients with typical and atypical morphology (3.03% versus 41.18%). No correlation was found between this alteration and the rest of the clinical and biological parameters studied (adenopathi es, hepatomegaly, splenomegaly, lymphocyte count, staging, CD11c expre ssion, and resistance to chemotherapy). The p53 deletion was correlate d with the presence of hepatomegaly and splenomegaly, advanced stage o f disease, and resistance to conventional chemotherapy. The applicatio n of FISH to whole blood cell nuclei, without prior manipulation or cu lture, showed a higher percentage of cells with trisomy 12 than when t he method was used following culture. We conclude that 1) FISH is a si mple and sensitive technique for the detection of numerical and struct ural chromosome abnormalities; 2) Its application to uncultured sample s obviates the alteration of results originated by the probable growth advantage of the normal or neoplastic cell population in vitro; 3) Tr isomy 12 appears to define a B-CLL subgroup of atypical morphology; an d 4) The p53 deletion is correlated with advanced stage of disease and resistance to treatment.