The molecular mechanism of chronic myelogenous leukemia and its therapeutic implications: studies in a murine model

被引:36
作者
Ren, RB [1 ]
机构
[1] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biol, Waltham, MA 02454 USA
关键词
CML; BCR-ABL; mouse model; signalling; oncogene cooperation;
D O I
10.1038/sj.onc.1206090
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic myelogenous leukemia (CML) is a malignant disease resulting from the neoplastic transformation of a hematopoietic stem cell. Generation of the BCR-ABL fusion gene plays an essential role in causing the vast majority of CML. Clinical and laboratory studies have indicated that development of CML involves both the effects of BCR-ABL within its correct target cells and interactions of BCR-ABL target cells with the rest of the in vivo environment, and that the progression of the disease to blast crisis involves multiple genetic alterations. An efficient mouse bone marrow transduction and transplantation model for CML has recently been developed. This review summarizes the analysis of the roles of functional domains and downstream signaling pathways of BCR-ABL, of altered cytokine production, of interferon signaling pathways and of oncogene cooperation in the pathogenesis of CML using this murine model. The in vivo studies of leukemogenesis will help to advance mechanism-based therapies for CML, as well as to understand fundamental rules of leukemogenesis and hematopoiesis.
引用
收藏
页码:8629 / 8642
页数:14
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