Runx3 deficiency results in myeloproliferative disorder in aged mice (Blood, June 2013)

The RUNX family genes encode transcription factors which are involved in development and human diseases. RUNX1 is one of the most frequently mutated genes in human hematological malignancies and is a critical factor for the generation and maintenance of hematopoietic stem cells. Another Runx family gene, Runx3, is known to be expressed in hematopoietic cells. However, its involvement in hematopoiesis remains unclear. Here we show the hematopoietic phenotypes in Runx3 conditional knockout (KO) mice (Runx3fl/fl;Mx1-Cre+): while young Runx3 KO mice did not exhibit any significant hematopoietic defects, aged Runx3 KO mice developed a myeloproliferative disorder characterized by myeloid-dominant leukocytosis, splenomegaly and an increase of hematopoietic stem/progenitor cells (HSPCs). Notably, Runx3-deficient cells showed hypersensitivity to granulocyte-colony stimulating factor (G-CSF), suggesting enhanced proliferative and mobilization capability of Runx3-deficient HSPCs when stimulated. These results suggest that, besides Runx1, Runx3 also plays a role in hematopoiesis.



Chelsia Qiuxia Wang 1,2, Lena Motoda 1, Masanobu Satake 3, Yoshiaki Ito 1,2, Ichiro, Taniuchi 5, Vinay Tergaonkar 1 and Motomi Osato 1,2,4,6,7

1Institute of Molecular and Cell Biology, Singapore
2Cancer Science Institute of Singapore, National University of Singapore
3Institute of Development, Aging and Cancer
4Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
5RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
6School of Biological Sciences, Nanyang Technological University, Singapore
7Institute of Bioengineering and Nanotechnology, Singapore

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