ISSN: 1300-7777 E-ISSN: 1308-5263
Variable Expression and Hypermethylation of p16 Gene in Patients with T-ALL and Cell Lines [Turk J Hematol]
Turk J Hematol. 2002; 19(3): 391-397

Variable Expression and Hypermethylation of p16 Gene in Patients with T-ALL and Cell Lines

Yusuf Özkul1, Ingrid Jurickova2, Harry W. W. Findley2
1Department Of Genetics, Medical Faculty, University Of Erciyes, Kayseri, Turkey
2Division Of Pediatric Hematology/oncology, Medical Faculty, University Of Emory, Atlanta, Ga, Usa

The multi tumor suppressor genes MTS1 (CDKN2, p16INK4A) and MTS2 (CDKN1, p15INK4B) located at 9p21-22 are inactivated in some human cancers via several mechanisms including deletion and hypermethylation. In hematological malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid malignancies, and more particularly to T-cell acute lymphoblastic leukemia (TALL). We have investigated the deletion, methylation and p16 protein expression status of MTS1 in Tcell childhood acute lymphoblastic leukemia (19 cases) and cell lines[11]. On Southern blot homozygous deletions or hemizygous deletion with rearangement were detected in 4/19 T-ALL. The expression of p16 protein was not observed on Western blot in 4/15 T-ALL with intact p16 gene. The p16 gene was methylated 3/15 in T-ALL. Only one of three expressed p16 protein. The other 11/15 T-ALL had p16 protein expression but different level. Loss of MTS1 was observed in 3/11 cell lines. Cell line with MTS1 gene had p16 protein expression in 6/8. After treatment with the demethylating agent (5-AzoCyt) RD cell line showed p16 expression. This has not been observed with the other cell lines. Thus hypermethylation of MTS1 is rare in childhood T-ALL. Although inactivation of MTS1 by deletion is common in T-ALL and cell lines. Furthermore our data show that the p16 gene inactivation by hypermethylation and deletion may play a role in the leukemogenesis.

Keywords: Tumor suppressor gene, p16, Acute lymphoblastic leukemia (ALL), Methylation, Expression.


Yusuf Özkul, Ingrid Jurickova, Harry W. W. Findley. Variable Expression and Hypermethylation of p16 Gene in Patients with T-ALL and Cell Lines. Turk J Hematol. 2002; 19(3): 391-397

Corresponding Author: Yusuf Özkul, Türkiye


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