TY - JOUR
T1 - Runx3 deficiency results in myeloproliferative disorder in aged mice
AU - Wang, Chelsia Qiuxia
AU - Motoda, Lena
AU - Satake, Masanobu
AU - Ito, Yoshiaki
AU - Taniuchi, Ichiro
AU - Tergaonkar, Vinay
AU - Osato, Motomi
N1 - Funding Information:
The authors thank K. Rajewshky for Mx-Cre Tg mice and members of the Biological Resource Center, Biopolis, and MD2 Vivarium, NUS, for mouse husbandry. This work was supported by the A*STAR (Agency of Science, Technology and Research), Biomedical Research Council, National Medical Research Council, Singapore National Research Foundation, and the Ministry of Education under the Research Center of Excellence Programme.
Funding Information:
This work was supported by the A*STAR (Agency of Science, Technology and Research), Biomedical Research Council, National Medical Research Council, Singapore National Research Foundation, and the Ministry of Education under the Research Center of Excellence Programme.
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/7/25
Y1 - 2013/7/25
N2 - The RUNX family genes encode transcription factors that 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+): whereas 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, 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.
AB - The RUNX family genes encode transcription factors that 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+): whereas 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, 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.
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U2 - 10.1182/blood-2012-10-460618
DO - 10.1182/blood-2012-10-460618
M3 - Article
C2 - 23741011
AN - SCOPUS:84886941879
SN - 0006-4971
VL - 122
SP - 562
EP - 566
JO - Blood
JF - Blood
IS - 4
ER -
