ArticleThe Journal of clinical investigation2000
Fatal myeloproliferation, induced in mice by TEL/PDGFbetaR expression, depends on PDGFbetaR tyrosines 579/581.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 112 citations in OpenAlex.
- Multiple allostery in the regulation of PDGFR beta kinase activities.Acta biochimica et biophysica Sinica · 2024Article
- A novel subclonal rearrangement of the STRN3::PDGFRB gene in de novo acute myeloid leukemia with NPM1 mutation and its leukemogenic effects.Cancer gene therapy · 2023Article
- The tyrosine phosphatase SHP2 is required for cell transformation by the receptor tyrosine kinase mutants FIP1L1-PDGFRα and PDGFRα D842V.Molecular oncology · 2014Article
- Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis.American journal of blood research · 2012Article
- Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells.The Journal of biological chemistry · 2011Article
- Structure of the AML1-ETO NHR3-PKA(RIIα) complex and its contribution to AML1-ETO activity.Journal of molecular biology · 2010Article
- Critical role of the platelet-derived growth factor receptor (PDGFR) beta transmembrane domain in the TEL-PDGFRbeta cytosolic oncoprotein.The Journal of biological chemistry · 2010Article
- Pathological interactions between hematopoietic stem cells and their niche revealed by mouse models of primary myelofibrosis.Expert review of hematology · 2009Article
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- Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage.Blood · 2007Article
- Neoplasia driven by mutant c-KIT is mediated by intracellular, not plasma membrane, receptor signaling.Molecular and cellular biology · 2007Article
- FLT3 is fused to ETV6 in a myeloproliferative disorder with hypereosinophilia and a t(12;13)(p13;q12) translocation.Leukemia · 2006Article
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- Review
- Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin.The Journal of clinical investigation · 2004Article
- Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease.The Journal of clinical investigation · 2004Article
- Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
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9 authors at 4 institutions in 1 country.
Funding
Abstract
The t(5;12)(q33;p13) translocation associated with chronic myelomonocytic leukemia (CMML) generates a TEL/PDGFbetaR fusion gene. Here, we used a murine bone marrow transplant (BMT) assay to test the transforming properties of TEL/PDGFbetaR in vivo. TEL/PDGFbetaR, introduced into whole bone marrow by retroviral transduction, caused a rapidly fatal myeloproliferative disease that closely recapitulated human CMML. TEL/PDGFbetaR transplanted mice developed leukocytosis with Gr-1(+) granulocytes, splenomegaly, evidence of extramedullary hematopoiesis, and bone marrow fibrosis, but no lymphoproliferative disease. We assayed mutant forms of the TEL/PDGFbetaR fusion protein - including 8 tyrosine to phenylalanine substitutions at phosphorylated PDGFbetaR sites to which various SH2 domain-containing signaling intermediates bind - for ability to transform hematopoietic cells. All of the phenylalanine (F-) mutants tested conferred IL-3-independence to a cultured murine hematopoietic cell line, but, in the BMT assay, different F-mutants displayed distinct transforming properties. In transplanted animals, tyrosines 579/581 proved critical for the development of myeloproliferative phenotype. F-mutants with these residues mutated showed no sign of myeloproliferation but instead developed T-cell lymphomas. In summary, TEL/PDGFbetaR is necessary and sufficient to induce a myeloproliferative disease in a murine BMT model, and PDGFbetaR residues Y579/581 are required for this phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.