Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

Nikola Curik, Pavel Burda, Karin Vargova, Vit Pospisil, Monika Belickova, Petra Vlckova, Filipp Savvulidi, Emanuel Necas, Hana Hajkova, Cedrik Haskovec, Jaroslav Cermak, Maria Krivjanska, Marek Trneny, Peter Laslo, Anna Jonasova, Tomas Stopka

. 2012 ; 26 (8) : 1804-1811.

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc13000946

Grant support
NS9634 MZ0 CEP Register
NS10310 MZ0 CEP Register
NS10632 MZ0 CEP Register

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 significant 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 significantly 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 modifications at the URE and cell differentiation outcome. Our data collectively support the importance of modifying the URE chromatin structure as a regulatory mechanism of AZA-mediated activation of PU.1 and induction of the myeloid program in MDS.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc13000946
003      
CZ-PrNML
005      
20141014171332.0
007      
ta
008      
130108s2012 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/leu.2012.47 $2 doi
035    __
$a (PubMed)22343522
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Čuřík, Nikola. $7 xx0230099 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
245    10
$a 5-azacitidine in aggressive myelodysplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity / $c Nikola Curik, Pavel Burda, Karin Vargova, Vit Pospisil, Monika Belickova, Petra Vlckova, Filipp Savvulidi, Emanuel Necas, Hana Hajkova, Cedrik Haskovec, Jaroslav Cermak, Maria Krivjanska, Marek Trneny, Peter Laslo, Anna Jonasova, Tomas Stopka
520    9_
$a 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 significant 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 significantly 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 modifications at the URE and cell differentiation outcome. Our data collectively support the importance of modifying the URE chromatin structure as a regulatory mechanism of AZA-mediated activation of PU.1 and induction of the myeloid program in MDS.
650    _2
$a senioři $7 D000368
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a protinádorové antimetabolity $x farmakologie $x terapeutické užití $7 D000964
650    _2
$a azacytidin $x farmakologie $x terapeutické užití $7 D001374
650    _2
$a buněčná diferenciace $x účinky léků $x genetika $7 D002454
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a chromatin $x genetika $7 D002843
650    _2
$a faktory stimulující kolonie $x farmakologie $7 D003115
650    _2
$a metylace DNA $x účinky léků $7 D019175
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a regulace genové exprese u leukemie $x účinky léků $7 D015973
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a myelodysplastické syndromy $x farmakoterapie $x genetika $7 D009190
650    _2
$a nádorové kmenové buňky $x cytologie $x účinky léků $x metabolismus $7 D014411
650    _2
$a protoonkogenní proteiny $x genetika $x metabolismus $7 D011518
650    _2
$a regulační oblasti nukleových kyselin $x účinky léků $7 D012045
650    _2
$a trans-aktivátory $x genetika $x metabolismus $7 D015534
650    _2
$a aktivace transkripce $x účinky léků $7 D015533
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Burda, Pavel $7 xx0172028 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Vargová, Karina $7 xx0172018 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Pospíšil, Vít $7 xx0128409 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Beličková, Monika $7 xx0099634 $u Institute of Hematology and Blood Transfusion, Prague, Czech Republic
700    1#
$a Vlčková, Petra $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Savvulidi, Filipp $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Nečas, Emanuel, $d 1943- $7 jk01082825 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic
700    1_
$a Hájková, Hana $7 xx0121176 $u Institute of Hematology and Blood Transfusion, Prague, Czech Republic
700    1_
$a Haškovec, Cedrik, $d 1943- $7 jk01040122 $u Institute of Hematology and Blood Transfusion, Prague, Czech Republic
700    1_
$a Čermák, Jaroslav $u Institute of Hematology and Blood Transfusion, Prague, Czech Republic
700    1_
$a Krivjanska, Maria $u KRD and CEBIOS, Prague, Czech Republic
700    1_
$a Trněný, Marek, $d 1960- $7 nlk20000083659 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic; Institute of Hematology and Blood Transfusion, Prague, Czech Republic; First Medical Department - Hematology, General Faculty Hospital, Prague, Czech Republic
700    1_
$a Laslo, Peter $u University of Leeds, United Kingdom
700    1_
$a Jonášová, Anna $7 xx0103767 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic; First Medical Department - Hematology, General Faculty Hospital, Prague, Czech Republic
700    1_
$a Stopka, Tomáš $7 xx0101300 $u First Faculty of Medicine, Institute of pathologic physiology, Charles University, Prague, Czech Republic; University of Leeds, United Kingdom
773    0_
$w MED00003138 $t Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K $x 1476-5551 $g Roč. 26, č. 8 (2012), s. 1804-1811
856    41
$u https://pubmed.ncbi.nlm.nih.gov/22343522 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20130108 $b ABA008
991    __
$a 20141014171724 $b ABA008
999    __
$a ok $b bmc $g 963728 $s 799110
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2012 $b 26 $c 8 $d 1804-1811 $i 1476-5551 $m Leukemia $n Leukemia $x MED00003138
GRA    __
$a NS9634 $p MZ0
GRA    __
$a NS10310 $p MZ0
GRA    __
$a NS10632 $p MZ0
LZP    __
$a Pubmed-20130108

Find record

Citation metrics

Archiving options