RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity

D. W.L. Chin, M. Sakurai, G. S.S. Nah, L. Du, B. Jacob, T. Yokomizo, T. Matsumura, T. Suda, G. Huang, X. Y. Fu, Y. Ito, H. Nakajima, M. Osato

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16 Citations (Scopus)


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.

Original languageEnglish
Article numbere379
JournalBlood cancer journal
Publication statusPublished - 2016 Jan 8

ASJC Scopus subject areas

  • Hematology
  • Oncology


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