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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F13%3A00422959%21RIV14-AV0-68378050
rdf:type
n7:Vysledek skos:Concept
dcterms:description
Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype. Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.
dcterms:title
Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia
skos:prefLabel
Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia
skos:notation
RIV/68378050:_____/13:00422959!RIV14-AV0-68378050
n7:predkladatel
n8:ico%3A68378050
n3:aktivita
n12:I n12:P
n3:aktivity
I, P(LK21307)
n3:cisloPeriodika
5
n3:dodaniDat
n11:2014
n3:domaciTvurceVysledku
Alberich-Jorda, Meritxell
n3:druhVysledku
n15:J
n3:duvernostUdaju
n5:S
n3:entitaPredkladatele
n18:predkladatel
n3:idSjednocenehoVysledku
106737
n3:idVysledku
RIV/68378050:_____/13:00422959
n3:jazykVysledku
n16:eng
n3:klicovaSlova
Sox4; C/EBP alpha; acute myeloid leukemia
n3:klicoveSlovo
n10:Sox4 n10:acute%20myeloid%20leukemia n10:C%2FEBP%20alpha
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[D4000E303901]
n3:nazevZdroje
Cancer Cell
n3:obor
n13:EB
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
21
n3:projekt
n14:LK21307
n3:rokUplatneniVysledku
n11:2013
n3:svazekPeriodika
24
n3:tvurceVysledku
Zhang, H. Welner, R. S. Hoogenkamp, M. Cammenga, J. Staber, P. B. Levantini, E. Bonifer, C. Valk, P. J. Amabile, G. Ye, M. Saez, B. Yang, H. Delwel, R. Ebralidze, A. Nerlov, C. Tenen, D. G. Alberich-Jorda, Meritxell Lefebvre, V. DiRuscio, A. Scadden, D. T. Zhang, J.
n3:wos
000327005100006
s:issn
1535-6108
s:numberOfPages
14
n6:doi
10.1016/j.ccr.2013.09.018