Morishita Kazuhiro
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
Int J Hematol. 2007 May;85(4):279-86. doi: 10.1532/IJH97.06174.
Leukemia is a group of monoclonal diseases that arise from hematopoietic stem and progenitor cells in the bone marrow or other hematopoietic organs. Retroviral infections are one of the major events leading to leukemogenesis in mice, because retroviruses can induce hematopoietic disease via the insertional mutagenesis of oncogenes; therefore, the cloning of viral-integration sites in murine leukemia has provided valuable molecular tags for oncogene discovery. Transcription of the murine gene ecotropic viral-integration site 1 (Evi1) is activated by nearby viral integration. In humans, the Evi1 homologue EVI1 is activated by chromosomal translocations. This review discusses the roles of the overexpression of EVI1/MEL1 gene family members in leukemogenesis, the relationships of various translocations in EVI1 overexpression, and the importance of PR domains in tumor suppression and oncogenesis. The functions of EVI1/MEL1 members as transcription factors and the concept of EVI1-positive leukemia as a stem cell disease are also reviewed.
白血病是一组起源于骨髓或其他造血器官中的造血干细胞和祖细胞的单克隆疾病。逆转录病毒感染是导致小鼠白血病发生的主要事件之一，因为逆转录病毒可通过致癌基因的插入诱变诱导造血疾病；因此，克隆小鼠白血病中的病毒整合位点为发现致癌基因提供了有价值的分子标记。小鼠嗜异性病毒整合位点1（Evi1）基因的转录因附近的病毒整合而被激活。在人类中，Evi1同源物EVI1通过染色体易位被激活。本综述讨论了EVI1/MEL1基因家族成员过表达在白血病发生中的作用、EVI1过表达中各种易位的关系，以及PR结构域在肿瘤抑制和肿瘤发生中的重要性。还综述了EVI1/MEL1成员作为转录因子的功能以及EVI1阳性白血病作为干细胞疾病的概念。
