Study On Tumor Suppressor Gene P53 And Its Antagonist Oncogene MDM2 In Acute Leukemia

Tumor suppressor gene p53 gene usually loses its normal function through point mutations and aellelic losses in human cancers. It is considered that inactivation of p53 gene is one of the commonest mechanisms in human tumourigenesis. However, mutations of p53 gene in acute lekemia are less frequent than that in other tumors. Oncogene MDM2,which acts as antagonist of p53 gene, is able to bind with p53 protein and thus abort its function to repress the emergency and development of tumor. Amplification and overexpression of MDM2 gene were found in some malignant tumors lacking mutations of p53 gene. It might be the case that amplification and overexpression of MDM2 gene are common events in acute leukemias, in which mutations of p53 gene are less frequent. We studied the status of the two genes and the relations between them in 41 acute leukemia patients and two leukemic cell lines-K051 and HL60.Our results demonstrate that1. Chromosome abnormalities were seen in 13 of 33 leukemia patients,but none of them involved 17p or 12q.2. No amplifications of MDM2 gene were found in all the patients and two cell lines when detected with Southern blotting and/or dot hybridization.3. By using Rt-PCR/SSCP, mutations of p53 gene were detected in 8 out of 41 acute leukemia patients. The incidence of the mutations was higher than those reported in literatures. p53 gene mutations showed no relations to FAB subtypes of acute leukemia and prognoses of the patients.4. By using Rt-PCR, overexpreession of MDM2 was detected in 21 patients out of the 41 patients and in cell line HL60 but not in cell line K051. Overexpression of MDM2 gene have relations to the prognoses of the patients but not to FAB subtype of leukemias and p53 gene mutations.Conclusion:1. No relationship between abnormalities of chromosomes 17p and/or 12q and changes of p53 gene and MDM2 gene was found in our patients,and p53 gene mutations were inversely proportional to overall chromosomal abnomalities;2.Mutations of p53 gene in acute leukemia are less frequent than that in other tumors, and showed no relations to FAB subtypes and prognoses of acute leukemias.3. Overexpression of MDM2 gene occured in over 50% of acute leukemia patients but no...