NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia.

Abstract	The myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis and dysplasia. A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene. Using a NUP98-HOXD13 fusion gene, we have developed a mouse model that faithfully recapitulates all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia, and apoptosis, and transformation to acute leukemia. The MDS that develops in NUP98-HOXD13 transgenic mice is uniformly fatal. Within 14 months, all of the mice died of either leukemic transformation or severe anemia and leucopenia as a result of progressive MDS. The NUP98-HOXD13 fusion gene inhibits megakaryocytic differentiation and increases apoptosis in the bone marrow, suggesting a mechanism leading to ineffective hematopoiesis in the presence of a hypercellular bone marrow. These mice provide an accurate preclinical model that can be used for the evaluation of MDS therapy and biology.
Authors	Ying-Wei Lin, Christopher Slape, Zhenhua Zhang, Peter D Aplan
Journal	Blood (Blood) Vol. 106 Issue 1 Pg. 287-95 (Jul 01 2005) ISSN: 0006-4971 [Print] United States
PMID	15755899 (Publication Type: Journal Article)
Chemical References	Carcinogens HOXD13 protein, human Homeodomain Proteins Hoxd13 protein, mouse Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins Nuclear Pore Complex Proteins Transcription Factors nuclear pore complex protein 98 Tetradecanoylphorbol Acetate
Topics	Acute Disease Animals Carcinogens (pharmacology) Cell Differentiation (drug effects, physiology) Cell Transformation, Neoplastic Disease Models, Animal Homeodomain Proteins (genetics) Humans K562 Cells Leukemia (genetics, physiopathology) Mice Mice, Inbred C57BL Mice, Transgenic Myelodysplastic Syndromes (genetics, physiopathology) Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins (genetics) Nuclear Pore Complex Proteins (genetics) Penetrance Phenotype Severity of Illness Index Tetradecanoylphorbol Acetate (pharmacology) Transcription Factors (genetics) Translocation, Genetic

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