Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome.
In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
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Daley
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Van Etten
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Baltimore
D000818:Animals; D001853:Bone Marrow / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004279:DNA, Viral / Q000302:isolation & purification; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009196:Myeloproliferative Disorders / Q000382:microbiology / Q000473:pathology; D010677:Philadelphia Chromosome; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000382:microbiology; D014161:Transduction, Genetic
D004273:DNA, Neoplasm; D004279:DNA, Viral; D016044:Fusion Proteins, bcr-abl