PROGNOSTIC IMPORTANCE OF P15(INK4B) AND PL6(INK4) GENE INACTIVATION IN CHILDHOOD ACUTE LYMPHOCYTIC-LEUKEMIA

Purpose: The present study explores the prognostic importance of p16(I NK4)/P15(INK4B) gene inactivation in childhood acute lymphocytic: leuk emia (ALL). Materials and Methods. Cells from 79 pediatric ALL patient s were investigated for inactivation of the p15(INK4B) and p16(INK4) g enes or loss of heterozygosity (LOH) for chromosome 9p markers by use of Southern hybridization, restriction fragment length polymorphism (R FLP) analysis, microsatellite analysis as well as single-strand confor mation polymorphism (SSCP) analysis, and nucleotide sequencing of the p15(INK4B) and p16(INK4) genes. Genetic data were correlated to clinic al outcome and established prognostic factors. Results: Inactivation o f the p15(INK4B) and/or p16(INK4) genes by homozygous deletion or loss of one allele and mutation of the other wets detected in 24 cases (30 %), Another 12 patients (15%) showed loss of one allele. A statistical ly significant correlation was found between inactivation of the p15(I NK4B)/p16(INK4) genes and poor prognosis (P < .01), Furthermore, inact ivation proved to be on independent factor that predicted relapse, ran king second to WBC count, The trend toward overrepresentation of treat ment failure was strongest in the high-risk (HR) group patients with p 16(INK4)/p15(INK4B) gene inactivation. Patients with deletion of genet ic material on 9p21 and normal coding sequence of the remaining p16(IN K4) and p15(INK4B) genes had a similar prognosis to that of nondeleted cases. Conclusion: The data suggest that analysis of p15(INK4B)/p16(I NK4) genes may contribute prognostic information in pediatric ALL. (C) 1996 by American Society of Clinical Oncology.