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  current news   Press   selected story    
     
  21st June 2013  
  Runx3 deficiency results in myeloproliferative disorder in aged mice
 
 




Authors
Chelsia Qiuxia Wang1,2, Lena Motoda1, Masanobu Satake3, Yoshiaki Ito1,2, Ichiro
Taniuchi5, Vinay Tergaonkar1,* and Motomi Osato1,2,4,6,7,*.

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

Published online in Blood on June 5, 2013.

Abstract

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.

Figure Legend: Aged Runx3 KO mice shows enhanced myeloproliferation with an expanded hematopoietic stem/progenitor cell (HSPC) compartment.

(A) Complete blood counts (CBC) performed on 18 months old Runx3 WT (n = 9) and Runx3 KO mice (n = 21).   White blood cell (WBC), hemoglobin (Hb) and platelet (Plt) counts are shown.  The statistical significance (p-value, student’s t-test) is shown at the top.

(B) May-Grünwald-Giemsa staining of peripheral blood (PB) cells in aged mice.  Representative pictures of cells are shown.

(C) Number of cells of each lineage in bone marrow (BM) of 18 months old mice.  Lineage markers: myeloid, Mac-1+ and Gr-1+; B-cells, B220+CD19+; T-cells, CD3+; erythroid, Ter119+.  Mean±SD are shown (WT, n = 2; KO, n = 4).  Three independent experiments were performed.  Asterisk(s) represents significant difference (**p < 0.01, student’s t-test).

(D) BM cellularity of aged mice.  Mean±SD of the numbers of cells in BM are shown (WT, n = 2; KO, n = 4).  Asterisk represents significant difference (**p < 0.01, student’s t-test).

(E) Spleen of aged Runx3 KO mice.  Left panel, graphical representation of spleen weight in the aged mice.  Mean±SD are shown (WT, n = 2; KO, n = 4).  Asterisk represents significant difference (*p < 0.05, student’s t-test).  Three independent experiments were performed.  Right panel, representative pictures of spleens in the aged mice.

For more information on Vinay TERGAONKAR's lab, please click here.