Animal models of chronic myelogenous leukemia

Of the current mouse chronic myelogenous leukemia (CML) models,the murine bone marrow (BM) transduction and transplantation model most efficiently mimics many of the central features of human CML. In this model, lethally irradiated mice are reconstituted with primary murine BM cells transduced with a P210BCR/ABL retrovirus. All recipient mice develop a fatal peripheral blood and BM granulocytosis and splenomegaly, a disease termed the murine CML-like myeloproliferative disorder. This model has been used to establish the causative role of Bcr/Abl in CML, identify those signaling pathways and regions of Bcr/Abl critical for leukemogenesis, and explore the limitations of targeted CML therapy. Future refinements in this CML mouse model will make it a more effective tool for studying imatinib-resistant CML, reproducing chronic- and blastic-phase human CML, and performing CML progenitor studies.