The equilibrium and control of cell proliferation, Survival and death in chronic hematological neoplasms

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In chronic hematological neoplasmas such as chronic lymphocytic leukemia (CLL) and chronic type of adult T-cell leukemia (ATL) , it is likely that cell proliferation, survival and death keep good equilibrium in each. The aim of this study is analysis of the relationship between cell prolifeartion and death, particulaly programd cell death(apoptosis), in order to clarify the pathological features and to find new approach to therapy in chronic hematological neoplasms. Firstly, we established the serum free culture system in which we can examine several factors assoiated with the apoptosis. In CLL and ATL, we found that apoptosis is increased by corticosteroid and protein kinase A activator and decreased by interleukin 2. In ATL, we detected the mutation and deletion of the p53 gene, which regulate cell cycle at the Gl check point and control apoptosis. The alteration of p53 gene is frequently observed in acute and crisis type of ATL but not in chronic type, suggesting that the p53 gene alteration is assosiated with disease progression.In addition, we found EBV genome as a single episomal form is 4 out of 34 patients with T-cell lymphoma and leukemia, indicating that latent gene products of EBV or celluler oncogenes are involved in the development of Japanese T-cell neoplasm following EBV infection. These observations indicate that the several inner and outer factors regulate cell proliferation and death in chronic hematological neoplasms.