We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics.
Aberrant expression of tumor suppressor genes WT 1, RB 1, p53, homozygous deletion of p16 gene and their relationship with expression of oncogenes BCR-ABL, TEL-AML 1, MLL-AF 4, E2A-PBX 1, SIL-TAL 1 were determined in bone marrow samples of children with de novo B-lineage (n=170) and T-lineage (n=25) acute lymphoblastic leukemia (ALL).
At diagnosis, p15 methylation occurred in 29 (58%) AML patients, and 10 (40.0%) ALL patients. p16 methylation occurred in two (4%) AML and two (8%) ALL patients.
The methylation-specific polymerase chain reaction (MS-PCR) was used to analyze p15 and p16 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML).
Our preliminary findings on eight pediatric patients with acute lymphoblastic leukemia (ALL) suggested that the survival of patients carrying a homozygous p16 gene deletion was significantly inferior to that of those without a deletion.
Finally, dexamethasone (Dex) induced apoptosis of JKB p16MT cells cultured at 40 degrees C, but did not trigger death of these cells cultured at 31 degrees C. These results suggest that deletion of p16 gene in JKB human ALL cells is associated with dysregulated growth of less differentiated tumor cells, which nonetheless remain susceptible to apoptosis triggered by Dex.
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.
We analyzed 60 B precursor acute lymphoblastic leukemia (ALL) primary samples and 15 cell lines for homozygous deletions of p16 and p15 genes and mutations of p16 gene.
Homozygous deletions of p16 exons were found in 5 of 10 (50%) patients with CML in lymphoid BC and in 5 (26%) ALL patients, but in only 1 (2%) case with AML.
Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot.