2016年1月
RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity
BLOOD CANCER JOURNAL
- 巻
- 6
- 号
- 開始ページ
- e379
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1038/bcj.2015.105
- 出版者・発行元
- NATURE PUBLISHING GROUP
RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1(+/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.
- リンク情報
- ID情報
-
- DOI : 10.1038/bcj.2015.105
- ISSN : 2044-5385
- PubMed ID : 26745853
- Web of Science ID : WOS:000369302100003