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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. (en)
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Title
| - C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
- C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia (en)
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skos:prefLabel
| - C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
- C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia (en)
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skos:notation
| - RIV/68378050:_____/12:00387490!RIV13-AV0-68378050
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http://linked.open...avai/predkladatel
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/68378050:_____/12:00387490
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - C/EBP transcription factor; acute myeloid leukemia; differentiation (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
| - Journal of Clinical Investigation
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Zhang, H.
- Alberich-Jorda, M.
- Amabile, G.
- Avellino, R.
- Balaštík, Martin
- Delwel, R.
- DiRuscio, A.
- Ebralidze, A. K.
- Figueroa, M. E.
- Lowers, I.
- Melcnick, A.
- Radomska, H. S.
- Shapiro-Koss, C.
- Tenen, D. G.
- Valk, P. J. M.
- Wouters, B.
- Ye, M.
- Zhang, J. Y.
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http://linked.open...ain/vavai/riv/wos
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issn
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number of pages
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http://bibframe.org/vocab/doi
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is http://linked.open...avai/riv/vysledek
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