Deletions of the p16 gene in pediatric leukemia and corresponding cell lines.
The p16 gene (MTS1 or CDK4I) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4), has been reported to be deleted in various tumor cell lines, including lines derived from leukemic cells. The reported frequency of p16 gene loss is much higher in established cell lines than in primary tumor specimens. We investigated the status of the p16 gene in pediatric leukemias using 12 established cell lines of differing phenotypes and their corresponding primary leukemic cells. Six of 12 cell lines, including acute lymphoblastic leukemia (ALL) lines of T-cell (three of four), of precursor-B cell (two of four) and of mixed phenotype (one of four), showed homozygous deletion of the p16 gene using PCR and Southern blotting. Comparison of the cell lines with their corresponding primary leukemic cells clearly showed that in all 12 paired samples there were identical findings with respect to the presence or absence of the p16 gene, demonstrating that loss of the gene was a feature of the primary leukemic cells. This is the first study to show this correlation using a panel of paired samples, indicating that p16 gene deletions were not an artifact of in vitro cell culture. Furthermore, the survival of ALL patients with p16 gene deletions was significantly inferior to those without deletions, suggesting that this genetic alteration may be a clinical prognostic factor.
Kees
U R
UR
Division of Children's Leukemia and Cancer Research, TVWT Institute for Child Health Research, Perth, Australia.
Ranford
P R
PR
Hatzis
M
M
D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015458:Leukemia, T-Cell / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16