Abstract
Chronic myelomonocytic leukemia (CMML) is a pre-leukemic syndrome that displays both myelodysplastic and myeloproliferative features. The t(5;12) chromosomal translocation, present in a subset of CMML patients with myeloproliferation fuses the amino terminal portion of the ets family member, Tel, with the transmembrane and tyrosine kinase domains of platelet-derived growth factor receptor β (PDGFRβ) gene. To investigate the role of this fusion protein in the pathogenesis of CMML, we expressed the Tel-PDGFRβ fusion cDNA in hematopoietic cells of transgenic mice under the control of the human CD11a promoter. Transgenic founders and their offspring express the transgene specifically in hematopoietic tissues and develop a myeloproliferative syndrome characterized by: overproduction of mature neutrophils and megakaryocytes in the bone marrow; splenomegaly with effacement of splenic architecture by extramedullary hematopoiesis; an abnormal population of leukocytes co-expressing lymphoid and myeloid markers; and increased numbers of colonies in in vitro bone marrow CFU assays. All mice expressing the transgene exhibited at least one of these features of dysregulated myelopoiesis, and 20% progressed to a myeloid or lymphoid malignancy. This murine model of CMML parallels a myeloproliferative syndrome in humans and implicates the Tel-PDGFRβ fusion protein in its pathogenesis.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes
Diagnostic Pathology Open Access 22 February 2012
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ritchie, K., Aprikyan, A., Bowen-Pope, D. et al. The Tel-PDGFRβ fusion gene produces a chronic myeloproliferative syndrome in transgenic mice. Leukemia 13, 1790–1803 (1999). https://doi.org/10.1038/sj.leu.2401494
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401494
Keywords
This article is cited by
-
Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes
Diagnostic Pathology (2012)
-
Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease
Oncogene (2002)
-
Mechanisms of Transformation by the BCR/ABL Oncogene
International Journal of Hematology (2001)
-
Tel induces a G1 arrest and suppresses Ras-induced transformation
Oncogene (2000)
-
Ets target genes: past, present and future
Oncogene (2000)