Studies on p16, p15, p18 and p19 Methylation of INK4 Series Cancer Inhibitive Gene in Leukemia

Objective To explore the correlation between the family of p16 gene inactiviation in generation, development and prognosis of leukemia, and then to clarify, the pathogenesis of leukemia, to inspect process of leukemia, to provide basis for gene therapy. Methods Methylation sensitive enzyme and polymerase chain reaction(PCR) technology were used to investigate p16, p15, p18, p19 gene methylation in leukemia. The subjects of the thesis were focused on the following aspects: (1)studies on homozygous deletion of the family of p16 exon 1 and/or exon 2 in leukemia with different type and different period; (2)methylation of the family of p16 gene was investigated in cases of leukemia by REP PCR. To explore methylation frequency on leukemia, and analyse the correlation between methylation of the family of p16 gene and generation of leukemia. Results Methylation rates of p16 and p15 gene exon 1 were 35 29% and 48 65% in acute leukemia(AL), respectively. It were found 60% and 69 23% in acute lymphoblastic leukemia(ALL), 25% and 37 5% in acute non lymphocytic leukemia(ANLL), 61 54% and 70 59% in relapsed AL, 29 09% and 42 10% in primary AL, respectively. There was no methylation in complete remission acute leukemia(CR AL) and the controls, in chromic period and blast crisis of chronic myelocyte leukemia(CML). There was no methylation of p18 and p19 gene in AL, chronic period and blast crisis of CML, CR AL, and the controls. Conclusion (1)In the family of p16 gene, methylation rates of p16 and p15 gene in ALL were higher than in ANLL. It were highest in replase cases, expecially. There was no methlation of p18 and p19 gene found in AL. (2)The methylation rate of p15 gene is higher than that in p16 gene. Methylation p16 and p15 gene in ANLL was higher than that in CR AL or the controls. (3)p16 and p15 gene inactiviation might be one of parameters for forecasting progression, relapse and prognosis in AL. (4)There is no relation in chronic period and blast crisis of CML with inactiviation of p16 and p15 gene.