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(INK4)/P15(INK4B) gene inactivation in childhood acute lymphocytic: leukemia (ALL). Materials and Methods. Cells from 79 pediatric ALL patients were investigated for inactivation of the p15(INK4B) and p16(INK4) genes or loss of heterozygosity (LOH) for chromosome 9p markers by use of Southern hybridization, restriction fragment length polymorphism (RFLP) analysis, microsatellite analysis as well as single-strand conformation polymorphism (SSCP) analysis, and nucleotide sequencing of the p15(INK4B) and p16(INK4) genes. Genetic data were correlated to clinical outcome and established prognostic factors. Results: Inactivation of 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 statistically significant correlation was found between inactivation of the p15(INK4B)/p16(INK4) genes and poor prognosis (P < .01), Furthermore, inactivation proved to be on independent factor that predicted relapse, ranking second to WBC count, The trend toward overrepresentation of treatment failure was strongest in the high-risk (HR) group patients with p16(INK4)/p15(INK4B) gene inactivation. Patients with deletion of genetic material on 9p21 and normal coding sequence of the remaining p16(INK4) and p15(INK4B) genes had a similar prognosis to that of nondeleted cases. Conclusion: The data suggest that analysis of p15(INK4B)/p16(INK4) genes may contribute prognostic information in pediatric ALL. (C) 1996 by American Society of Clinical Oncology.