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Modeling Philadelphia chromosome positive leukemias Wong S; Witte ONOncogene 2001[Sep]; 20 (40): 5644-59The 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.|Animals[MESH]|Bone Marrow Cells/metabolism[MESH]|Cell Differentiation[MESH]|Fusion Proteins, bcr-abl/genetics/metabolism[MESH]|Genetic Linkage[MESH]|Humans[MESH]|Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/*physiopathology[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Mice, Transgenic[MESH]|Models, Genetic[MESH]|Oncogene Proteins, Fusion/metabolism[MESH]|Phenotype[MESH]|Promoter Regions, Genetic[MESH]|Protein Structure, Tertiary[MESH]|Retroviridae/genetics[MESH]|Transduction, Genetic[MESH] |
