TitleGenetic and epigenetic heterogeneity in acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2016
AuthorsLi, Sheng, Mason Christopher E., and Melnick Ari
JournalCurr Opin Genet Dev
Volume36
Pagination100-6
Date Published2016 Feb
ISSN1879-0380
KeywordsDNA Methylation, Epigenesis, Genetic, Genetic Heterogeneity, Genome, Human, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Mutation
Abstract

<p>Genetic and epigenetic heterogeneity is emerging as a fundamental property of human cancers. Reflecting the genesis of tumors as an evolutionary process driven by clonal selection. The complexity of clonal architecture has been known for many years in the setting of acute myeloid leukemia (AML), based on karyotyping studies. However the true complexity of AMLs is only now being understood thanks to in depth genome sequencing studies in humans, which reveal that heterogeneity is a multilayered and involves not only the genome but also the epigenome. Here, we review recent advances in genetic and epigenetic heterogeneity and clonal dynamics in AML and their relevance to biology, clinical outcomes and therapeutic implications. Special attention is focused on somatic mutations affecting regulators of cytosine methylation, since these tend to occur early in disease evolution, reprogram the epigenome of hematopoietic stem cells, and are linked to unfavorable outcome.</p>

DOI10.1016/j.gde.2016.03.011
Alternate JournalCurr Opin Genet Dev
PubMed ID27162099
PubMed Central IDPMC4903929
Grant ListR01 NS076465 / NS / NINDS NIH HHS / United States