Prognostic importance of p15INK4B and p16INK4 gene inactivation in childhood acute lymphocytic leukemia.
OBJECTIVE
The present study explores the prognostic importance of p16INK4/p15INK4B gene inactivation in childhood acute lymphocytic leukemia (ALL).


METHODS
Cells from 79 pediatric ALL patients were investigated for inactivation of the p15INK4B and p16INK4 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 p15INK4B and p16INK4 genes. Genetic data were correlated to clinical outcome and established prognostic factors.


RESULTS
Inactivation of the p15INK4B and/or p16INK4 genes by homozygous deletion or loss of one allele and mutation of the other was detected in 24 cases (30%). Another 12 patients (15%) showed loss of one allele. A statistically significant correlation was found between inactivation of the p15INK4B/p16INK4 genes and poor prognosis (P < .01). Furthermore, inactivation proved to be an 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 p16INK4/p15INK4B gene inactivation. Patients with deletion of genetic material on 9p21 and normal coding sequence of the remaining p16INK4 and p15INK4B genes had a similar prognosis to that of nondeleted cases.


CONCLUSIONS
The data suggest that analysis of p15INK4B/p16INK4 genes may contribute prognostic information in pediatric ALL.
Heyman
M
M
Radiumhemmet, Stockholm, Sweden.
Rasool
O
O
Borgonovo Brandter
L
L
Liu
Y
Y
Grandér
D
D
Söderhäll
S
S
Gustavsson
G
G
Einhorn
S
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D017211:Treatment Failure
D015342:DNA Probes; D004273:DNA, Neoplasm