Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease

B. R. Baldwin, Li Li, K. F. Tse, S. Small, M. Collector, Katharine Whartenby, S. J. Sharkis, F. Racke, D. Huso, Donald Small

Research output: Contribution to journalArticle

Abstract

Evidence is continuing to accumulate that the FMS-like tyrosine kinase 3 (FLT3) receptor plays an important role in acute leukemias. Acute myeloid leukemia patients often express constitutive active mutant forms of the receptor in their leukemic cells. A t(12;13)(p13;q12) translocation between Tel and the FLT3 receptor was recently described in a patient with myeloproliferative disease (MPD). Here a Tel-FLT3 construct mimicking this fusion protein was used to generate transgenic mice. The fusion protein was previously found to constitutively activate FLT3 signaling and transform Ba/F3 cells. Expression of the fusion protein in the transgenic mice was found in all tissues assayed including spleen, bone marrow (BM), thymus and liver. These mice developed splenomegaly and had a high incidence of MPD with extramedullary hematopoiesis in the liver and lymph nodes. Spleens also had increased dendritic and natural killer cell populations. In vitro analysis of the hematopoietic progenitor cells derived from Tel-FLT3 transgenic mice showed a significant increase in the number of CFU-GM in the BM, and CFU-GM, BFU-E and CFU-GEMM in the spleen. BM also showed significant increases of in vivo CFU-S colonies. Thus, transgenic mice expressing constitutively activated Tel-FLT3 develop MPD with a long latency and also result in the expansion of the hematopoietic stem/progenitor cells.

Original languageEnglish (US)
Pages (from-to)764-771
Number of pages8
JournalLeukemia
Volume21
Issue number4
DOIs
StatePublished - Apr 2007

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Protein-Tyrosine Kinases
Transgenic Mice
Hematopoietic Stem Cells
Granulocyte-Macrophage Progenitor Cells
Spleen
Bone Marrow
Receptor Protein-Tyrosine Kinases
Extramedullary Hematopoiesis
Myeloid Progenitor Cells
Erythroid Precursor Cells
Proteins
Liver
Splenomegaly
Acute Myeloid Leukemia
Natural Killer Cells
Thymus Gland
Leukemia
Lymph Nodes
Incidence
Population

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease. / Baldwin, B. R.; Li, Li; Tse, K. F.; Small, S.; Collector, M.; Whartenby, Katharine; Sharkis, S. J.; Racke, F.; Huso, D.; Small, Donald.

In: Leukemia, Vol. 21, No. 4, 04.2007, p. 764-771.

Research output: Contribution to journalArticle

Baldwin, B. R. ; Li, Li ; Tse, K. F. ; Small, S. ; Collector, M. ; Whartenby, Katharine ; Sharkis, S. J. ; Racke, F. ; Huso, D. ; Small, Donald. / Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease. In: Leukemia. 2007 ; Vol. 21, No. 4. pp. 764-771.
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