BACKGROUND: The expression of mutant p53 seems to induce malignant transformation by blocking the progression of cell differentiation or apoptotic process. The purpose of this study was to investigate the role of apoptosis and, possibly, a mutant p53 in ineffective hematopoiesis in myelodysplastic syndrome(MDS). The role of the mutant p53 in the leukemic transformation was also studied. METHODS: The bone marrow sections were prepared from 41 patients with MDS, 20 patients with acute myelogenous leukemia(AML) and 10 normal controls. The degree of apoptosis and the overexpression of p53 were evaluated using in situ end-labelling (ISEL) and immunohistochemical staining, respectively. RESULTS: Apoptosis was significantly increased in MDS(P<0.01 vs controls), while AML showed decreased apoptosis (P<0.01 vs controls). Overexpression of p53 protein was observed in 7 (17.1%) of 41 MDS and 3 (15.0%) of 20 AML patients, while it was not increased in normal controls. There were no p53 overexpression in all patients with normal karyotype. However, p53 overexpression was found in 5 out of 10 patients with abnormal karyotype. Three of 5 patients with p53 overexpression showed weak positive staining, and 2 with strong positive staining had complete or partial loss of 17p. CONCLUSION: These findings suggest that apoptosis has a role in ineffective hematopoiesis in MDS. The apoptosis is remarkably decreased in patients with AML. Mutation of p53 may contribute to transformation. Further systemic studies using more cases would be needed to obtain objective assessment data that immunohistochemical examination for p53 overexpression is considered to be useful in predicting the evolution to overt leukemia from MDS in the future.
Abnormal Karyotype ; Apoptosis* ; Bone Marrow ; Cell Differentiation ; Hematopoiesis ; Humans ; Karyotype ; Leukemia ; Leukemia, Myeloid, Acute* ; Myelodysplastic Syndromes*