Journal article
TEL/PDGFβR Induces Hematologic Malignancies in Mice That Respond to a Specific Tyrosine Kinase Inhibitor
Blood, Vol.93(5), pp.1707-1714
03/01/1999
DOI: 10.1182/blood.V93.5.1707.405k24_1707_1714
PMID: 10029600
Abstract
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 protein tyrosine kinases associated with hematopoietic malignancies, TEL/PDGFβR is invariably associated with a myeloid leukemia phenotype in humans. To test the transforming properties of TEL/PDGFβR in vivo, and to analyze the basis for myeloid lineage specificity in humans, we constructed transgenic mice with TEL/PDGFβR expression driven by a lymphoid-specific immunoglobulin enhancer-promoter cassette. These mice developed lymphoblastic lymphomas of both T and B lineage, demonstrating that TEL/PDGFβR is a transforming protein in vivo, and that the transforming ability of this fusion is not inherently restricted to the myeloid lineage. Treatment of TEL/PDGFβR transgenic animals with a protein tyrosine kinase inhibitor with in vitro activity against PDGFβR (CGP57148) resulted in suppression of disease and a prolongation of survival. A therapeutic benefit was apparent both in animals treated before the development of overt clonal disease and in animals transplanted with clonal tumor cells. These results suggest that small-molecule tyrosine kinase inhibitors may be effective treatment for activated tyrosine kinase–mediated malignancies both early in the course of disease and after the development of additional transforming mutations.
Details
- Title: Subtitle
- TEL/PDGFβR Induces Hematologic Malignancies in Mice That Respond to a Specific Tyrosine Kinase Inhibitor
- Creators
- Michael H Tomasson - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORIfor R Williams - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORRobert Hasserjian - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORChirayu Udomsakdi - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORShannon M McGrath - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORJuerg Schwaller - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORBrian Druker - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, ORD. Gary Gilliland - From the Division of Hematology, Brigham and Women’s Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, OR
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.93(5), pp.1707-1714
- DOI
- 10.1182/blood.V93.5.1707.405k24_1707_1714
- PMID
- 10029600
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 03/01/1999
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094666102771
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