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

在慢性血液肿瘤如慢性淋巴细胞性白血病（CLL）和慢性型成人T细胞白血病（ATL）中，细胞增殖、存活和死亡可能在每一种中保持良好的平衡。本研究的目的是分析细胞增殖与死亡，特别是程序性细胞死亡（凋亡）的关系，以阐明慢性血液肿瘤的病理特点，为慢性血液肿瘤的治疗寻找新的途径。首先，我们建立了无血清培养体系，在此体系中我们可以检测与细胞凋亡相关的几个因素。在CLL和ATL中，我们发现皮质类固醇和蛋白激酶A激活剂可增加细胞凋亡，而白细胞介素2可减少细胞凋亡。在ATL中，我们检测到p53基因的突变和缺失，其在G1检查点调节细胞周期并控制凋亡。p53基因的改变在急性和危象型ATL中较常见，而在慢性型ATL中则不常见，提示p53基因的改变与疾病的进展有关，另外，我们在34例T细胞淋巴瘤和白血病患者中发现4例EBV基因组为单一的附加型，表明EBV或细胞癌基因的潜伏基因产物参与EBV感染后日本T细胞肿瘤的发展。这些观察结果表明，在慢性血液肿瘤细胞增殖和死亡的几个内部和外部因素调节。

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.