5-azacytidine in aggressive myelodysplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F26424991%3A_____%2F12%3A%230000010" target="_blank" >RIV/26424991:_____/12:#0000010 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

5-azacytidine in aggressive myelodysplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity

Popis výsledku v původním jazyce

Epigenetic 5-azacitidine (AZA) therapy of high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) represents a promising, albeit not fully understood, approach. Hematopoietic transcription factor PU.1 is dynamically regulated by upstream regulatory element (URE), whose deletion causes downregulation of PU.1 leading to AML in mouse. In this study a signi?cant group of the high-risk MDS patients, as well as MDS cell lines, displayed downregulation of PU.1 expression within CD34 ? cells, which was associated with DNA methylation of the URE. AZA treatment in vitro signi?cantly demethylated URE, leading to upregulation of PU.1 followed by derepression of its transcriptional targets and onset of myeloid differentiation. Addition of colony-stimulating factors (CSFs; granulocyte-CSF, granulocyte -- macrophage-CSF and macrophage-CSF) modulated AZA-mediated effects on reprogramming of histone modi?cations at the URE and cell differentiation outcome. Our data collectively s

Název v anglickém jazyce

5-azacytidine in aggressive myelodysplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity

Popis výsledku anglicky

Epigenetic 5-azacitidine (AZA) therapy of high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) represents a promising, albeit not fully understood, approach. Hematopoietic transcription factor PU.1 is dynamically regulated by upstream regulatory element (URE), whose deletion causes downregulation of PU.1 leading to AML in mouse. In this study a signi?cant group of the high-risk MDS patients, as well as MDS cell lines, displayed downregulation of PU.1 expression within CD34 ? cells, which was associated with DNA methylation of the URE. AZA treatment in vitro signi?cantly demethylated URE, leading to upregulation of PU.1 followed by derepression of its transcriptional targets and onset of myeloid differentiation. Addition of colony-stimulating factors (CSFs; granulocyte-CSF, granulocyte -- macrophage-CSF and macrophage-CSF) modulated AZA-mediated effects on reprogramming of histone modi?cations at the URE and cell differentiation outcome. Our data collectively s

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/FR-TI2%2F509" target="_blank" >FR-TI2/509: *Vývoj kitu na testování účinosti protinádorové léčby ovlivňující strukturu jaderného chromatinu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Leukemia

ISSN

0887-6924

e-ISSN

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Svazek periodika

2012

Číslo periodika v rámci svazku

26

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

1804-1811

Kód UT WoS článku

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EID výsledku v databázi Scopus

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