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Epigenetic aberrations in acute myeloid leukemia: Early key events during leukemogenesis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Karolinska Inst, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
2015 (English)In: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 43, no 8, 609-624 p.Article in journal (Refereed) Published
Abstract [en]

As a result of the introduction of new sequencing technologies, the molecular landscape of acute myeloid leukemia (AML) is rapidly evolving. From karyotyping, which detects only large genomic aberrations of metaphase chromosomes, we have moved into an era when sequencing of each base pair allows us to define the AML genome at highest resolution. This has revealed a new complex landscape of genetic aberrations where addition of mutations in epigenetic regulators has been one of the most important contributions to the understanding of the pathogenesis of AML. These findings, together with new insights into epigenetic mechanisms, have placed dysregulated epigenetic mechanisms at the forefront of AML development. Not only have several new mutations in genes directly involved in epigenetic regulatory mechanisms been discovered, but also previously well-known gene fusions have been found to exert aberrant effects through epigenetic mechanisms. In addition, mutations in epigenetic regulators such as DNMT3A, TET2, and ASXL1 have recently been found to be the earliest known events during AML evolution and to be present as preleukemic lesions before the onset of AML. In this article, we review epigenetic changes in AML also in relation to what is known about their mechanism of action and their prognostic role.

Place, publisher, year, edition, pages
2015. Vol. 43, no 8, 609-624 p.
National Category
Hematology
Identifiers
URN: urn:nbn:se:uu:diva-263035DOI: 10.1016/j.exphem.2015.05.009ISI: 000360321900003PubMedID: 26118500OAI: oai:DiVA.org:uu-263035DiVA: diva2:857535
Available from: 2015-09-29 Created: 2015-09-24 Last updated: 2017-12-01Bibliographically approved

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Eriksson, AnnaLehmann, Sören

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