PRESENCE OF A P53 GENE DELETION IN PATIENTS WITH MULTIPLE-MYELOMA PREDICTS FOR SHORT SURVIVAL AFTER CONVENTIONAL-DOSE CHEMOTHERAPY

(I)n multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in si tu hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, w hich were found to be predominantly monoallelic, were detected in 32.8 % and 54.5% of patients with newly diagnosed and relapsed MM, respecti vely. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 lo cus) provided evidence for an interstitial deletion on 17p resulting i n loss of p53 hybridization signals in myeloma cells. Among all 59 pat ients with newly diagnosed MM, presence of a p53 deletion was associat ed with stage III (P =.054), but not with other laboratory and clinica l parameters. Patients with a p53 deletion had significantly shorter s urvival time compared with those without a deletion, both from the tim e of diagnosis [median 13.9 v38.7 months; P <.0001) and from the time of initiation of induction treatment consisting of conventional dose c hemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression analysis, presence of a p5 3 deletion was the most significant independent parameter predicting f or shortened survival (P =.002). We conclude that a p53 gene deletion, which can be identified by interphase FISH in almost a third of patie nts with newly diagnosed MM, is a novel prognostic factor predicting f or short survival of MM patients treated with conventional-dose chemot herapy. (C) 1998 by The American Society of Hematology.