Molecular mechanism of leukemogenesis in ATL

对ATL病例HTLV-1前病毒的分析表明，约60%的病例不表达Tax。ATL患者HTLV-1前病毒除HBZ基因外，其余基因均存在无义突变，且在整合前由APOBEC3G产生。此外，在ATL病例中，HTLV-1前病毒5‘LTR区的缺失也发生在整合前。提示HBZ基因在ATL中的意义。HBZ基因转录本在所有ATL病例中均有表达，并具有促生长活性。HBZ转基因小鼠出现T细胞淋巴瘤和炎症性疾病，提示HBZ基因在HTLV-1致病机制中起核心作用。

Analyses of HTLV-1 provirus in ATL cases showed that Tax was not expressed in about 60% of cases. Nonsense mutations in HTLV-1 provirus of ATL cases were found in all viral genes except HBZ gene, and generated by APOBEC3G before integration. In addition, deletion of 5'LTR of HTLV-1 provirus in ATL cases also occurred before integration. These findings suggest significance of HBZ gene in ATL cases. The HBZ gene transcript was found in all ATL cases, and had growth-promoting activity. In HBZ transgenic mice, T-cell lymphomas and inflammatory diseases occurred, indicating that HBZ gene plays a central role in the pathogenesis by HTLV-1.