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

Oncogene volume 21, pages 8629–8642 (2002)Cite this article

Abstract

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.

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Acknowledgements

I thank Alec W Gross and Ramesh Subrahmanyam for their critical reading of this review. This work was supported by National Cancer Institute grant CA68008 and by ACS Grant RSG-02-059-01-LIB. R Ren is a recipient of The Leukemia and Lymphoma Society Scholar Award.

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    Ruibao Ren

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Ren, R. The molecular mechanism of chronic myelogenous leukemia and its therapeutic implications: studies in a murine model. Oncogene 21, 8629–8642 (2002). https://doi.org/10.1038/sj.onc.1206090

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