Modeling Philadelphia chromosome positive leukemias.
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.
Wong
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Molecular Biology Institute, University of California, Los Angeles, California, CA 90095-1662, USA.
Witte
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D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D008040:Genetic Linkage; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D015514:Oncogene Proteins, Fusion; D016044:Fusion Proteins, bcr-abl