Please use this identifier to cite or link to this item:
https://doi.org/10.1038/bcj.2015.105
DC Field | Value | |
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dc.title | RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity | |
dc.contributor.author | Chin, D.W.L | |
dc.contributor.author | Sakurai, M | |
dc.contributor.author | Nah, G.S.S | |
dc.contributor.author | Du, L | |
dc.contributor.author | Jacob, B | |
dc.contributor.author | Yokomizo, T | |
dc.contributor.author | Matsumura, T | |
dc.contributor.author | Suda, T | |
dc.contributor.author | Huang, G | |
dc.contributor.author | Fu, X.-Y | |
dc.contributor.author | Ito, Y | |
dc.contributor.author | Nakajima, H | |
dc.contributor.author | Osato, M | |
dc.date.accessioned | 2020-09-10T01:43:07Z | |
dc.date.available | 2020-09-10T01:43:07Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Chin, 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.issn | 20445385 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/175447 | |
dc.description.abstract | 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. © 2016, Nature Publishing Group. All rights reserved. | |
dc.publisher | Nature Publishing Group | |
dc.source | Unpaywall 20200831 | |
dc.subject | granulocyte colony stimulating factor | |
dc.subject | granulocyte macrophage colony stimulating factor | |
dc.subject | interleukin 3 | |
dc.subject | interleukin 6 | |
dc.subject | protein Pias3 | |
dc.subject | regulator protein | |
dc.subject | STAT3 protein | |
dc.subject | transcription factor RUNX1 | |
dc.subject | unclassified drug | |
dc.subject | chaperone | |
dc.subject | chemokine receptor CXCR4 | |
dc.subject | cytokine | |
dc.subject | granulocyte colony stimulating factor | |
dc.subject | PIAS3 protein, human | |
dc.subject | protein binding | |
dc.subject | protein inhibitor of activated STAT | |
dc.subject | STAT3 protein | |
dc.subject | transcription factor RUNX1 | |
dc.subject | animal cell | |
dc.subject | animal experiment | |
dc.subject | Article | |
dc.subject | bone marrow cell | |
dc.subject | cell differentiation | |
dc.subject | controlled study | |
dc.subject | haploinsufficiency | |
dc.subject | hematopoiesis | |
dc.subject | hematopoietic cell | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | in vitro study | |
dc.subject | leukemogenesis | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | point mutation | |
dc.subject | protein expression | |
dc.subject | protein phosphorylation | |
dc.subject | protein protein interaction | |
dc.subject | signal transduction | |
dc.subject | stem cell expansion | |
dc.subject | stem cell mobilization | |
dc.subject | thrombocyte disorder | |
dc.subject | acute myeloid leukemia | |
dc.subject | animal | |
dc.subject | disease model | |
dc.subject | drug effects | |
dc.subject | drug resistance | |
dc.subject | gene expression regulation | |
dc.subject | genetic predisposition | |
dc.subject | genetics | |
dc.subject | genotype | |
dc.subject | hematopoietic stem cell | |
dc.subject | metabolism | |
dc.subject | mutation | |
dc.subject | pathology | |
dc.subject | phosphorylation | |
dc.subject | Animals | |
dc.subject | Blood Platelet Disorders | |
dc.subject | Bone Marrow Cells | |
dc.subject | Core Binding Factor Alpha 2 Subunit | |
dc.subject | Cytokines | |
dc.subject | Disease Models, Animal | |
dc.subject | Drug Resistance | |
dc.subject | Gene Expression Regulation, Leukemic | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Genotype | |
dc.subject | Granulocyte Colony-Stimulating Factor | |
dc.subject | Haploinsufficiency | |
dc.subject | Hematopoietic Stem Cells | |
dc.subject | Humans | |
dc.subject | Leukemia, Myeloid, Acute | |
dc.subject | Mice | |
dc.subject | Molecular Chaperones | |
dc.subject | Mutation | |
dc.subject | Phosphorylation | |
dc.subject | Protein Binding | |
dc.subject | Protein Inhibitors of Activated STAT | |
dc.subject | Receptors, CXCR4 | |
dc.subject | Signal Transduction | |
dc.subject | STAT3 Transcription Factor | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | DEPT OF MEDICINE | |
dc.contributor.department | DEPT OF BIOCHEMISTRY | |
dc.description.doi | 10.1038/bcj.2015.105 | |
dc.description.sourcetitle | Blood Cancer Journal | |
dc.description.volume | 6 | |
dc.description.page | e379 | |
Appears in Collections: | Staff Publications Elements |
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