Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marksVisa övriga samt affilieringar
2011 (Engelska)Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 20, s. 5573-5582Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
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.
Ort, förlag, år, upplaga, sidor
American Society of Hematology , 2011. Vol. 118, nr 20, s. 5573-5582
Nationell ämneskategori
Hematologi
Identifikatorer
URN: urn:nbn:se:oru:diva-22580DOI: 10.1182/blood-2011-01-332353ISI: 000297265400028PubMedID: 21960591Scopus ID: 2-s2.0-81555214615OAI: oai:DiVA.org:oru-22580DiVA, id: diva2:516603
Forskningsfinansiär
CancerfondenBarncancerfondenVetenskapsrådet
Anmärkning
Funding Agencies:
Göran Gustafssons Foundation for Research in Natural Sciences
Sigurd och Elsa Golje Foundation
Ligue Contre le Cancer
La Region Pays de la Loire/Appel a Projets du Canceropole Grand-Ouest
2012-04-182012-04-182018-05-03Bibliografiskt granskad