Abstract
Both p16 and p15, encoded by genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases (CDK4/6) and upstream regulators of retinoblastoma protein (Rb) function. Methylation is an important mechanism for the inactivation of the p16 and p15 genes. To investigate whether these genes are inactivated by methylation of the 5'CpG islands of the genes, we examined 11 lymphoid cell lines and 18 primary lymphoid malignancies (malignant lymphoma and acute lymphoblastic leukemia) by Southern blotting analysis. The p16 gene was methylated in 3 of 11 lymphoid cell lines, whereas the p15 gene was methylated in 6 of 11 cell lines. Deletions of these genes occurred in 4 of 11 cell lines. T cell lineage leukemia cell lines tended to be deleted, and B cell lineage leukemia cell lines tended to be methylated frequently. In primary lymphoid malignancies, methylation of the p16 gene was rare in malignant lymphoma, but in acute lymphoblastic leukemia, the gene was methylated in 4 of 5 cases. Moreover, in one case, methylation of the p16 was not observed at diagnosis but was observed at relapse. In the only case of acute lymphoblastic leukemia in which we examined exon 1 of the p15, it was deleted. These results indicate that p16 and p15 gene methylation could be an important mechanism of inactivation of these genes in lvmnhoid malignancies.
