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Modeling Philadelphia chromosome positive leukemias

Abstract

The Ph chromosome has been genetically linked to CML and ALL. Its chimeric fusion gene product, BCR–ABL, can generate leukemia in mice. This review will discuss selected model systems developed to study BCR–ABL induced leukemia and focuses on what we have learned about the human disease from these models. Five main experimental approaches will be discussed including: (i) Reconstitution of mice with bone marrow cells retrovirally transduced with BCR–ABL; (ii) Transgenic mice expressing BCR–ABL; (iii) Knock-in mice with BCR–ABL expression driven from the endogenous bcr locus; (iv) Development of CML-like disease in mice with loss of function mutations in heterologous genes; and (v) ES in vitro hematopoietic differentiation coupled with regulated BCR–ABL expression.

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Acknowledgements

We thank Dr Janusz HS Kabarowski and Lu Quang Le for helpful discussions and critical reading of this manuscript and JC White for the preparation of this manuscript. Work from this laboratory described in the manuscript was supported by funds from the National Cancer Institute and the Howard Hughes Medical Institute.

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Wong, S., Witte, O. Modeling Philadelphia chromosome positive leukemias. Oncogene 20, 5644–5659 (2001). https://doi.org/10.1038/sj.onc.1204638

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