Animal models of CML

Several experimental approaches have demonstrated the ability of BCR-ABL to cause leukemia. In one set of experiments, transgenic mice that express BCR-ABL were shown to develop a rapidly fatal acute leukemia. Using a different approach, a BCR-ABL-expressing retrovirus was used to infect murine bone marrow. These BCR-ABL-expressing marrow cells were used to repopulate irradiated mice. The transplanted mice developed a variety of myeloproliferative disorders, including a CML-like syndrome. Although these approaches demonstrate the leukemogenic potential of BCR-ABL, it is possible that secondary changes are required for leukemia to develop. Recently, C. Huettner and colleagues placed BCR-

ABL under the control of a tetracydine-repressible promoter. Mice expressing this transgene develop a reversible leukemia dependent on the presence or absence of tetracycline, thus demonstrating the leukemic potential of BCR-ABL as a sole oncogenic abnormality.

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