逆转录病毒介导的髓系白血病小鼠模型研究的最新进展  

Recent Progress of Study on Retroviral Mediated Mouse Model of Myeloid Leukemia——Review

作　　者：施琳[1,2] 王月英[2] 陈赛娟[1,2] 

机构地区：[1]上海交通大学系统生物医学研究院,上海200240 [2]上海交通大学医学院附属瑞金医院上海血液学研究所,上海200025

出　　处：《中国实验血液学杂志》2011年第4期1058-1063,共6页Journal of Experimental Hematology

摘　　要：白血病的发生与多种遗传学异常如染色体易位和基因突变等密切相关,建立携带这些遗传学异常的小鼠模型是研究白血病发病机制和靶向治疗的有力工具。通过逆转录病毒介导的小鼠模型的建立,证实在急性髓系白血病(AML)中,AML1-ETO、PML-RARα、NUP98-HOX和MLL-AF9等融合基因与疾病的发生发展密切相关,还发现额外的遗传学异常能与AML中常见融合基因协同作用导致小鼠发生AML,如C-KIT N822K与AML1-ETO、FLT3-ITD与PML-RARα、Meis1与NUP98-HOX的协同作用。在慢性髓系性白血病(CML)中,BCR/ABL融合基因可使小鼠诱发CML,但CML急性变的发生还需要其他遗传学异常如GATA-2L359V、Hes1高表达等的参与。此外,对CML小鼠的治疗实验发现,伊马替尼和硫化砷两药合用具有更好的疗效。本文将对上述逆转录病毒介导的髓系白血病小鼠模型研究的最新进展进行综述,并讨论影响逆转录病毒介导的白血病小鼠模型成功建立的一些因素如逆转录病毒载体的构建、逆转录病毒滴度和造血微环境等。Human leukemia is closely associated with various genetic alterations such as chromosomal translocations and gene mutations. The use of retroviral transduction/bone marrow transplantation mouse model harboring these genetic abnormalities has been critical in understanding the molecular pathogenesis of leukemia and exploring new therapeutic target. Additional genetic events are verified to cooperate with fusion genes resulting from chromosomal translocations in acute myeloid leukemia （AML） to develop a leukemic phenotype in mice, such as C-KIT N822K with AML1-ETO, FLT3-ITD with PML-RARα, Meisl with NUP98-HOX, and Cdx4 with MLL-AF9. Mouse model shows that BCR/ABL fusion gene induces chronic myeloid leukemia （ CML）, and suggests that GATA-2 L359V and high expression of Hesl are key molecules in acute myeloid transformation of CML. Furthermore, combination therapy with Imatinib and arsenic sulfide for CML mice exerts more profound therapeutic effects than either drug as a single agent. This review focuses the recent progress and application of retroviral-mediated mouse models of myeloid leukemia, and discusses some factors influencing the mouse model establishment, including retroviral construction, retrovirus titer and hematopoietic

关 键 词：髓系白血病 小鼠模型 逆转录病毒 遗传学异常 

分 类 号：R733.7[医药卫生—肿瘤]