Blast Crisis in a Murine Model of Chronic Myelogenous Leukemia

The P210bcr/ablprotein is produced in cells from patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Retroviral transfer of the gene encoding P210bcr/ablinto murine bone marrow induces a granulocytic leukemia that models the chronic phase of human CML. We have transferred the leukemic clone to syngeneic animals, albeit with surprising inefficiency, and have observed CML and clonally related acute leukemias of lymphoid or myeloid phenotype in some transplant recipients. These data show that murine CML can result from retroviral transfer of the bcr/abl gene into pluripotent hematopoietic stem cells, that infected clones repopulate poorly after adoptive transfer, and that these clones can give rise to acute leukemia, reflecting evolution to a phase resembling blast crisis in the human disease.