TEL/PDGFβR Induces Hematologic Malignancies in Mice That Respond to a Specific Tyrosine Kinase Inhibitor

摘要: The TEL/PDGFβR fusion protein is expressed as the consequence of a recurring t(5;12) translocation associated with chronic myelomonocytic leukemia (CMML). Unlike other activated tyrosine kinases hematopoietic malignancies, invariably myeloid phenotype in humans. To test transforming properties vivo, and to analyze basis for lineage specificity humans, we constructed transgenic mice expression driven by lymphoid-specific immunoglobulin enhancer-promoter cassette. These developed lymphoblastic lymphomas both T B lineage, demonstrating that ability this not inherently restricted lineage. Treatment animals kinase inhibitor vitro activity against PDGFβR (CGP57148) resulted suppression disease prolongation survival. A therapeutic benefit was apparent treated before development overt clonal transplanted tumor cells. results suggest small-molecule inhibitors may be effective treatment kinase–mediated malignancies early course after additional mutations.