Apoptosis, Expression of p53 and p21 in Patients with Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Lee, Jung Soo; Hong, Ki Sook; Chung, Wha Soon; Lee, Soon Nam

Abstract

BACKGROUND
Apoptosis and its dysregulation have been implicated in dysplastic and ineffective hematopoiesis and the neoplastic transformation of bone marrow in myelodysplastic syndrome (MDS). The mutant p53 expression may induce malignant transformation by blocking the progression of cell differentiation or apoptotic process. The p21 protein can mediate p53-associated growth arrest and apoptosis. The purpose of this study was to elucidate the role of apoptosis, p53, and p21 in the development of MDS and acute myelogenous leukemia (AML).
METHODS
Paraffin-sections of bone marrow biopsies from 24 cases of MDS, 31 cases of AML, and 17 controls without malignant pathological alterations were investigated. Among the MDS patients, 6 patients were transformed to AML, they were classified as MDS-AML. The degree of apoptosis was evaluated by TUNEL method and the expression of p53 and p21 were evaluated by immunohistochemistry.
RESULTS
Apoptosis was significantly increased in MDS than de novo AML (P=0.011), MDS-AML (P<0.001) and controls (P=0.024). Overexpression of p53 was significantly increased in MDS-AML than MDS, de novo AML, and controls (P=0.010, P=0.032, P<0.001). Overexpression of p53 was also significantly increased in advanced MDS than early MDS (P=0.040). Expression of p21 was significantly increased in MDS and MDS-AML than de novo AML (P=0.012, P=0.011). No correlation between apoptosis, p53, and p21 was noticed in MDS, while positive correlation was noted between p53 and apoptosis, and p21 and apoptosis in de novo AML (P=0.032, P<0.001). In patients with MDS-AML, apoptosis was significantly decreased, but the positivity in the immunohistochemistry for p53 and p21 was not changed significantly during the process of transformation.
CONCLUSION
These findings suggest that increased apoptosis has a role in the pathogenesis of MDS and loss of apoptosis may be a prerequisite for the malignant trasnsformation into AML. Even though mutant p53 expression is not so common in MDS, it can be a prognostic factor indicating higher probability of transformation to AML. And the different patterns of p53 and p21 protein expressions suggest that there may be a derangement of the growth suppressive pathway involving these proteins, but they may be expressed by independent activation pathways.