C/EBP? deregulation results in differentiation arrest in acute myeloid leukemia
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F12%3A00387490" target="_blank" >RIV/68378050:_____/12:00387490 - isvavai.cz</a>
Výsledek na webu
<a href="http://dx.doi.org/10.1172/JCI65102" target="_blank" >http://dx.doi.org/10.1172/JCI65102</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/JCI65102" target="_blank" >10.1172/JCI65102</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
C/EBP? deregulation results in differentiation arrest in acute myeloid leukemia
Popis výsledku v původním jazyce
C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBP? is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBP? hypermethylation/silencing. Similarly, C/EBP? was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBP?, as C/EBP? mediates C/EBP? suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBP?-C/EBP? balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBP? mediates the myeloid differentiation arrest induced by C/EBP? deficiency and that targeting the C/EBP?-C/EBP? axis rescues neutrophilic diff
Název v anglickém jazyce
C/EBP? deregulation results in differentiation arrest in acute myeloid leukemia
Popis výsledku anglicky
C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBP? is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBP? hypermethylation/silencing. Similarly, C/EBP? was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBP?, as C/EBP? mediates C/EBP? suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBP?-C/EBP? balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBP? mediates the myeloid differentiation arrest induced by C/EBP? deficiency and that targeting the C/EBP?-C/EBP? axis rescues neutrophilic diff
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
EB - Genetika a molekulární biologie
OECD FORD obor
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Návaznosti výsledku
Projekt
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Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2012
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Clinical Investigation
ISSN
0021-9738
e-ISSN
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Svazek periodika
122
Číslo periodika v rámci svazku
12
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
15
Strana od-do
4490-4504
Kód UT WoS článku
000311926200024
EID výsledku v databázi Scopus
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