CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemiaReportar como inadecuado




CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemia - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Hematology and Oncology

, 7:66

First Online: 30 September 2014Received: 25 March 2014Accepted: 06 September 2014DOI: 10.1186-s13045-014-0066-4

Cite this article as: Hájková, H., Fritz, M.HY., Haškovec, C. et al. J Hematol Oncol 2014 7: 66. doi:10.1186-s13045-014-0066-4

Abstract

BackgroundStudying DNA methylation changes in the context of structural rearrangements and point mutations as well as gene expression changes enables the identification of genes that are important for disease onset and progression in different subtypes of acute myeloid leukemia AML patients. The aim of this study was to identify differentially methylated genes with potential impact on AML pathogenesis based on the correlation of methylation and expression data.

MethodsThe primary method of studying DNA methylation changes was targeted bisulfite sequencing capturing approximately 84 megabases Mb of the genome in 14 diagnostic AML patients and a healthy donors- CD34+ pool. Subsequently, selected DNA methylation changes were confirmed by 454 bisulfite pyrosequencing in a larger cohort of samples. Furthermore, we addressed gene expression by microarray profiling and correlated methylation of regions adjacent to transcription start sites with expression of corresponding genes.

ResultsHere, we report a novel hypomethylation pattern, specific to CBFB-MYH11 fusion resulting from inv16 rearrangement that is associated with genes previously described as upregulated in inv16 AML. We assume that this hypomethylation and corresponding overexpresion occurs in the genes whose function is important in inv16 leukemogenesis. Further, by comparing all targeted methylation and microarray expression data, PBX3 differential methylation was found to correlate with its gene expression. PBX3 has been recently shown to be a key interaction partner of HOX genes during leukemogenesis and we revealed higher incidence of relapses in PBX3-overexpressing patients.

ConclusionsWe discovered new genomic regions with aberrant DNA methylation that are associated with expression of genes involved in leukemogenesis. Our results demonstrate the potential of the targeted approach for DNA methylation studies to reveal new regulatory regions.

KeywordsAcute myeloid leukemia CBFB-MYH11 DNA methylation Targeted bisulfite sequencing PBX3 Electronic supplementary materialThe online version of this article doi:10.1186-s13045-014-0066-4 contains supplementary material, which is available to authorized users.

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