Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen

Hasemann, Marie Sigurd; Damgaard, Inge; Schuster, Mikkel Bruhn; Theilgaard‐Mönch, Kim; Sørensen, Annette Balle; Mrsic, Alan; Krugers, Thijs; Ylstra, Bauke; Pedersen, Finn Skou; Nerlov, Claus; Porse, Bo T.

doi:10.1182/blood-2007-06-097790

Cited by 11 publications

(11 citation statements)

References 59 publications

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“…47 We found several common integration sites and integrations of the retroviruses in the intron of MN1 in 2 of 15 cases examined (supplemental Table 1). Considering the recent works published by Hasemann et al 48 and by ourselves, 40 retrovirus integration might in part influence the phenotypes of the recipient mice in our BMT models. For example, integration of the retrovirus vector into MN1 may enhance cell growth.…”

Section: Transduction With C/ebp␣-c M Into Bm Cells Caused Aml In a Mmentioning

confidence: 88%

Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models

Kato

Kitaura

Doki

et al. 2011

Blood

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Section: Transduction With C/ebp␣-c M Into Bm Cells Caused Aml In a Mmentioning

confidence: 88%

Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models

Kato

Kitaura

Doki

et al. 2011

Blood

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“…61 Leukemic blasts from Cebpa biallelic mutant knockin mice share an identical gene expression program with these MLL-AF9-transduced leukemic GMPs. 62 Collectively, these findings indicate that a myeloid differentiation program is required to initiate myeloid leukemia.…”

Section: C/ebpa In Aml Initiation and Developmentmentioning

confidence: 95%

Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation

Avellino

Delwel

2017

Blood

136

110

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One of the most studied transcription factors in hematopoiesis is the leucine zipper CCAAT-enhancer binding protein α (C/EBPα), which is mainly involved in cell fate decisions for myeloid differentiation. Its involvement in acute myeloid leukemia (AML) is diverse, with patients frequently exhibiting mutations, deregulation of gene expression, or alterations in the function of C/EBPα. In this review, we emphasize the importance of C/EBPα for neutrophil maturation, its role in myeloid priming of hematopoietic stem and progenitor cells, and its indispensable requirement for AML development. We discuss that mutations in the open reading frame of CEBPA lead to an altered C/EBPα function, affecting the expression of downstream genes and consequently deregulating myelopoiesis. The emerging transcriptional mechanisms of CEBPA are discussed based on recent studies. Novel insights on how these mechanisms may be deregulated by oncoproteins or mutations/variants in CEBPA enhancers are suggested in principal to reveal novel mechanisms of how CEBPA is deregulated at the transcriptional level.

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“…Hematoxylin-eosin (HE) staining of fetal and adult liver sections was performed as described previously [38]. For the staining of livers for accumulation of lipids fixed slides was incubated 8 min.…”

Section: Methodsmentioning

confidence: 99%

UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration

et al. 2010

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BackgroundNonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues.Methodology/Principal FindingsHere we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration.Conclusion/SignificanceCollectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology.

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Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen

Abstract: The CCAAT enhancer binding protein ␣ (C/EBP␣) is an important myeloid tumor suppressor that is frequently mutated in human acute myeloid leukemia (AML

Cited by 11 publications

References 59 publications

Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models

Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models

Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation

UPF2 Is a Critical Regulator of Liver Development, Function and Regeneration

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