Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): Relation to disease status

Various genetic abnormalities are often found in B-CLL, but their relative importance in the pathogenesis and evolution of the disease has not been ad equately clarified. We studied the expression of bcl-2 protein and the poss ible simultaneous occurrence of bcl-2 overexpression, trisomy 12 and the Rb l and p53 gene deletions in 38 patients with B-CLL by combining immunopheno typing and dual color interphase FISH. We also looked for correlation betwe en the genetic abnormalities and clinical parameters such as stage, disease duration from diagnosis to the time of study and overall survival. High ex pression of the bcl-2 protein was found in 76.3% of the patients (29/38). T risomy 12 was found in 37% of cases (14/38) and Rbl monoallelic gene deleti on in 42% (16/38). The percentage of cells with hemizygous Rbl deletion ran ged from 13 to 18%. Monoallelic deletion of p53 was found in 29% of cases ( 11/38). The number of cells with only one signal ranged from 28 to 98%. Pat ients in stage A had on average, less than one abnormality, while patients in stage C had 2.6 abnormalities. Patients appeared to accumulate genetic a bnormalities with time. Bcl-2 overexpression was found early in the course of the disease. Trisomy 12 appeared later, at about the same time as Rbl de letion, but was not associated with adverse prognosis. Monoallelic deletion of p53 gene appeared rather late in the course of the disease and was asso ciated with advanced stage. Despite the fact that more deaths occurred in t he group of patients with three or four abnormalities and the presence of p 53 gene deletion, differences in survival were not statistically significan t, probably due to the limited number of patients in each group. A larger g roup of patients studied in a prospective manner will better clarify these issues in the future.