P53 GENE DELETION PREDICTS FOR POOR SURVIVAL AND NONRESPONSE TO THERAPY WITH PURINE ANALOGS IN CHRONIC B-CELL LEUKEMIAS

Conventional cytogenetic analysis in B-cell chronic lymphocytic leukem ia (B-CLL) has been very difficult, and the prognostic significance of specific chromosome aberrations is under discussion. Recent improveme nts in fluorescence in situ hybridization (ISH) techniques have provid ed an alternative approach for the detection of chromosome aberrations . Here, an interphase cytogenetic study was performed to analyze the i ncidence and prognostic significance of a p53 gene deletion in B-CLL a nd related disorders. We studied mononuclear cells from 100 patients w ith chronic B-cell leukemias [B-CLL, 90 patients; B-prolymphocytic leu kemia (B-PLL), 7; Waldenstrom's macroglobulinemia (WM), 3] by fluoresc ence ISH with a genomic p53 DNA probe. In a subset of patients, additi onal G-banding analysis and single strand conformation polymorphism (S SCP) analysis was performed. Seventeen of the 100 patients [17%; B-CLL , 11 of 90 (12%); WM, 1 of 3; B-PLL, 5 of 7] exhibited a monoallelic p 53 gene deletion by ISH. G-banding analysis demonstrated abnormalities of chromosome 17 in 13 of these 17 patients, all leading to loss of b and 17p13. SSCP analysis showed aberrant bands in 9 of 14 patients wit h a p53 gene deletion. None of 12 patients with a p53 gene deletion co mpared with 20 of 36 patients (56%) without a deletion responded to th erapy with fludarabine or pentostatin (P < .001). The difference in su rvival probabilities from the time of diagnosis and from the start of treatment with purine analogs between the two groups was highly signif icant (P < .001). In multivariate analysis, p53 gene deletion was the strongest prognostic factor for survival. In conclusion, p53 gene dele tion predicts for nonresponse to therapy with purine analogs and for p oor survival in chronic B-cell leukemias. (C) 1995 by The American Soc iety of Hematology.