Please use this identifier to cite or link to this item: https://doi.org/10.1038/bcj.2015.105
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dc.titleRUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity
dc.contributor.authorChin, D.W.L
dc.contributor.authorSakurai, M
dc.contributor.authorNah, G.S.S
dc.contributor.authorDu, L
dc.contributor.authorJacob, B
dc.contributor.authorYokomizo, T
dc.contributor.authorMatsumura, T
dc.contributor.authorSuda, T
dc.contributor.authorHuang, G
dc.contributor.authorFu, X.-Y
dc.contributor.authorIto, Y
dc.contributor.authorNakajima, H
dc.contributor.authorOsato, M
dc.date.accessioned2020-09-10T01:43:07Z
dc.date.available2020-09-10T01:43:07Z
dc.date.issued2016
dc.identifier.citationChin, D.W.L, Sakurai, M, Nah, G.S.S, Du, L, Jacob, B, Yokomizo, T, Matsumura, T, Suda, T, Huang, G, Fu, X.-Y, Ito, Y, Nakajima, H, Osato, M (2016). RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity. Blood Cancer Journal 6 : e379. ScholarBank@NUS Repository. https://doi.org/10.1038/bcj.2015.105
dc.identifier.issn20445385
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175447
dc.description.abstractRUNX1/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. © 2016, Nature Publishing Group. All rights reserved.
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectgranulocyte colony stimulating factor
dc.subjectgranulocyte macrophage colony stimulating factor
dc.subjectinterleukin 3
dc.subjectinterleukin 6
dc.subjectprotein Pias3
dc.subjectregulator protein
dc.subjectSTAT3 protein
dc.subjecttranscription factor RUNX1
dc.subjectunclassified drug
dc.subjectchaperone
dc.subjectchemokine receptor CXCR4
dc.subjectcytokine
dc.subjectgranulocyte colony stimulating factor
dc.subjectPIAS3 protein, human
dc.subjectprotein binding
dc.subjectprotein inhibitor of activated STAT
dc.subjectSTAT3 protein
dc.subjecttranscription factor RUNX1
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectArticle
dc.subjectbone marrow cell
dc.subjectcell differentiation
dc.subjectcontrolled study
dc.subjecthaploinsufficiency
dc.subjecthematopoiesis
dc.subjecthematopoietic cell
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectleukemogenesis
dc.subjectmouse
dc.subjectnonhuman
dc.subjectpoint mutation
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectprotein protein interaction
dc.subjectsignal transduction
dc.subjectstem cell expansion
dc.subjectstem cell mobilization
dc.subjectthrombocyte disorder
dc.subjectacute myeloid leukemia
dc.subjectanimal
dc.subjectdisease model
dc.subjectdrug effects
dc.subjectdrug resistance
dc.subjectgene expression regulation
dc.subjectgenetic predisposition
dc.subjectgenetics
dc.subjectgenotype
dc.subjecthematopoietic stem cell
dc.subjectmetabolism
dc.subjectmutation
dc.subjectpathology
dc.subjectphosphorylation
dc.subjectAnimals
dc.subjectBlood Platelet Disorders
dc.subjectBone Marrow Cells
dc.subjectCore Binding Factor Alpha 2 Subunit
dc.subjectCytokines
dc.subjectDisease Models, Animal
dc.subjectDrug Resistance
dc.subjectGene Expression Regulation, Leukemic
dc.subjectGenetic Predisposition to Disease
dc.subjectGenotype
dc.subjectGranulocyte Colony-Stimulating Factor
dc.subjectHaploinsufficiency
dc.subjectHematopoietic Stem Cells
dc.subjectHumans
dc.subjectLeukemia, Myeloid, Acute
dc.subjectMice
dc.subjectMolecular Chaperones
dc.subjectMutation
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectProtein Inhibitors of Activated STAT
dc.subjectReceptors, CXCR4
dc.subjectSignal Transduction
dc.subjectSTAT3 Transcription Factor
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.doi10.1038/bcj.2015.105
dc.description.sourcetitleBlood Cancer Journal
dc.description.volume6
dc.description.pagee379
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