Induction of Chronic Myelogenous Leukemia in Mice by the P210 ^{<i>bcr/abl</i>} Gene of the Philadelphia Chromosome

TLDR

The Philadelphia chromosome in chronic myelogenous leukemia cells encodes the P210 bcr/abl protein, a protein‑tyrosine kinase similar to the Abelson virus oncogene. To determine whether P210 bcr/abl can induce chronic myelogenous leukemia. Murine bone marrow was infected with a retrovirus encoding P210 bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed a myeloproliferative syndrome resembling human chronic myelogenous leukemia, and tumor tissue contained the P210 bcr/abl provirus, demonstrating that its expression induces CML and providing a murine model for further study.

Abstract

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 P210 bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210 bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160 gag /v- abl , which induces acute lymphomas. To determine whether P210 bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210 bcr/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 P210 bcr/abl . These results demonstrate that P210 bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.