Clinical Significance of p53 Protein Overexpression and Serum Anti-p53 Antibodies in Patients with Acute and Chronic Leukemia

Park, Jeong Seon; Park, Tae Hee; Lim, Young Tak; Jeong, Ju Seop; Lee, Eun Yup; Cho, Goon Jae

Abstract

BACKGROUND: Mutations of p53 gene, rarely found in leukemia, result in accumulation of mutated p53 protein in the nuclei of tumor cells, which can be detected by immunohistochemistry. Lately, anti-p53 antibodies were found in the sera of patients who had solid tumors as a result of immune response to accumulation of mutated p53 protein in tumor cells.
METHODS
For investigation of the clinical implication of cellular p53 protein overexpression and serum p53 antibody, immunohistochemical staining for p53 protein of B-5 fixed paraffin embedded bone marrow biopsies and enzyme immunoassay for the presence of anti-p53 antibodies of sera were performed simultanously; in 58 cases of AML, 34 cases of ALL, 11 cases of acute leukemia at relapse, 13 cases of CML in chronic phase and 5 cases of CLL.
RESULTS
Overexpression of p53 protein was found in 9.1%(11/121) of all leukemias, with 8.6% of AML with predominance of M6, 5.9% of ALL, 18.2% of acute leukemia at relapse and 40% of CLL, but not found in CML. Serum anti-p53 antibodies were found in 5.8%(7/121) of all leukemias, with 6.9% of AML and 5.9% of ALL, 9.1% of acute leukemia at relapse, but not found in chronic leukemias. In AML and ALL, age, sex, hemoglobin, leukocyte count, platelet count and blast % were not related with p53 protein expression. The AML patients with p53 protein overexpression have more unfavorable karyotypes(complex karyotype, -5, -7 and t(10;11)), with shorter overall survival as compared to those without p53 protein overexpression. The presence of serum anti-p53 antibodies was not related with clinical findings of leukemias.
CONCLUSIONS
The indications are that p53 gene alterations will contribute to disease development and progression in some specific patients with leukemia, due to the rare frequency of overexpression of p53 protein and serum anti-p53 antibodies in leukemia. Analysis of the p53 protein and serum p53 antibodies could screen p53 gene mutation and predict prognosis for some leukemias.