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Prognostic DNA meth...
Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks
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- Deneberg, Stefan (författare)
- Karolinska Institutet
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- Guardiola, Philippe (författare)
- Inserm, Angers, France; Service des Maladies du Sang, Centre Hospitalier Universitaire, Angers, France
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- Lennartsson, Andreas (författare)
- Karolinska Institutet
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- Qu, Ying (författare)
- Karolinska Institutet
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- Gaidzik, Verena E. (författare)
- Department of Internal Medicine III, University Hospital, Ulm, Germany
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- Blanchet, Odile (författare)
- Inserm, Angers, France; Laboratoire d Hematologie, Centre Hospitalier Universitaire, Angers, France
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- Karimi, Mohsen (författare)
- Karolinska Institutet
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- Bengtzén, Sofia (författare)
- Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
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- Nahi, Hareth (författare)
- Karolinska Institutet
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- Uggla, Bertil, 1962- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Hematology, Örebro University Hospital, Örebro, Sweden
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- Tidefelt, Ulf, 1951- (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Department of Hematology, Örebro University Hospital, Örebro, Sweden
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- Höglund, Martin (författare)
- Uppsala universitet,Medicin,Hematologi
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- Paul, Christer (författare)
- Department of Internal Medicine/Hematology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
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- Ekwall, Karl (författare)
- Karolinska Institutet
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- Döhner, Konstanze (författare)
- Department of Internal Medicine III, University Hospital, Ulm, Germany
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- Lehmann, Sören (författare)
- Karolinska Institutet
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(creator_code:org_t)
- American Society of Hematology, 2011
- 2011
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:20, s. 5573-5582
- Relaterad länk:
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https://ashpublicati...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- art (ämneskategori)
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Blood
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- Av författaren/redakt...
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Deneberg, Stefan
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Guardiola, Phili ...
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Lennartsson, And ...
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Qu, Ying
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Gaidzik, Verena ...
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Blanchet, Odile
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Karimi, Mohsen
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Bengtzén, Sofia
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Nahi, Hareth
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Uggla, Bertil, 1 ...
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Tidefelt, Ulf, 1 ...
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Höglund, Martin
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Paul, Christer
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Ekwall, Karl
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Döhner, Konstanz ...
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Lehmann, Sören
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Hematologi
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Blood
- Av lärosätet
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Örebro universitet
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Uppsala universitet
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Karolinska Institutet