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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F12%3A00387490%21RIV13-AV0-68378050
rdf:type
n5:Vysledek skos:Concept
dcterms:description
C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ 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/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs. C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ 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/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.
dcterms:title
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
skos:prefLabel
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
skos:notation
RIV/68378050:_____/12:00387490!RIV13-AV0-68378050
n5:predkladatel
n6:ico%3A68378050
n4:aktivita
n8:I
n4:aktivity
I
n4:cisloPeriodika
12
n4:dodaniDat
n14:2013
n4:domaciTvurceVysledku
n18:8764611
n4:druhVysledku
n11:J
n4:duvernostUdaju
n13:S
n4:entitaPredkladatele
n16:predkladatel
n4:idSjednocenehoVysledku
126173
n4:idVysledku
RIV/68378050:_____/12:00387490
n4:jazykVysledku
n17:eng
n4:klicovaSlova
C/EBP transcription factor; acute myeloid leukemia; differentiation
n4:klicoveSlovo
n12:differentiation n12:acute%20myeloid%20leukemia n12:C%2FEBP%20transcription%20factor
n4:kodStatuVydavatele
US - Spojené státy americké
n4:kontrolniKodProRIV
[4B89C2C08975]
n4:nazevZdroje
Journal of Clinical Investigation
n4:obor
n10:EB
n4:pocetDomacichTvurcuVysledku
1
n4:pocetTvurcuVysledku
18
n4:rokUplatneniVysledku
n14:2012
n4:svazekPeriodika
122
n4:tvurceVysledku
Balaštík, Martin Amabile, G. Melcnick, A. Ye, M. Lowers, I. Avellino, R. DiRuscio, A. Wouters, B. Radomska, H. S. Zhang, H. Shapiro-Koss, C. Alberich-Jorda, M. Tenen, D. G. Zhang, J. Y. Figueroa, M. E. Delwel, R. Valk, P. J. M. Ebralidze, A. K.
n4:wos
000311926200024
s:issn
0021-9738
s:numberOfPages
15
n7:doi
10.1172/JCI65102