Journal article
Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require granulocyte-macrophage colony-stimulating factor or interleukin-3
Blood, Vol.97(5), pp.1435-1441
03/01/2001
DOI: 10.1182/blood.V97.5.1435
PMID: 11222391
Abstract
Tyrosine kinase fusion oncogenes that occur as a result of chromosomal translocations have been shown to activate proliferative and antiapoptotic pathways in leukemic cells, but the importance of autocrine and paracrine expression of hematopoietic cytokines in leukemia pathogenesis is not understood. Evidence that leukemic transformation may be, at least in part, cytokine dependent includes data from primary human leukemia cells, cell culture experiments, and murine models of leukemia. This report demonstrates that interleukin (IL)-3 plasma levels are elevated in myeloproliferative disease (MPD) caused by the TEL/tyrosine kinase fusions TEL/platelet-derived growth factor beta receptor (PDGFβR), TEL/Janus kinase 2 (JAK2), and TEL/neurotrophin-3 receptor (TRKC). Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were elevated by TEL/PDGFβR and TEL/JAK2. However, all of the fusions tested efficiently induced MPD in mice genetically deficient for both GM-CSF and IL-3, demonstrating that these cytokines are not necessary for the development of disease in this model system. Furthermore, in experiments using normal marrow transduced with TEL/PDGFβR retrovirus mixed with marrow transduced with an enhanced green fluorescent protein (EGFP) retrovirus, the MPD induced in these mice demonstrated minimal stimulation of normal myelopoiesis by the TEL/PDGFβR-expressing cells. In contrast, recipients of mixed GM-CSF–transduced and EGFP-transduced marrow exhibited significant paracrine expansion of EGFP-expressing cells. Collectively, these data demonstrate that, although cytokine levels are elevated in murine bone marrow transplant models of leukemia using tyrosine kinase fusion oncogenes, GM-CSF and IL-3 are not required for myeloproliferation by any of the oncogenes tested.
Details
- Title: Subtitle
- Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require granulocyte-macrophage colony-stimulating factor or interleukin-3
- Creators
- Michael H Tomasson - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MAIfor R Williams - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MAShaoguang Li - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MAJeffrey Kutok - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MADanielle Cain - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MASilke Gillessen - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MAGlenn Dranoff - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MARichard A Van Etten - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MAD. Gary Gilliland - From the Division of Hematology, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Center for Blood Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; and the Howard Hughes Medical Institute, Boston, MA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.97(5), pp.1435-1441
- DOI
- 10.1182/blood.V97.5.1435
- PMID
- 11222391
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 03/01/2001
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094753502771
Metrics
16 Record Views