Format

Send to

Choose Destination
Curr Opin Genet Dev. 2016 Feb;36:100-6. doi: 10.1016/j.gde.2016.03.011. Epub 2016 May 7.

Genetic and epigenetic heterogeneity in acute myeloid leukemia.

Author information

1
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA.
2
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA; The Feil Family Brain and Mind Research Institute (BMRI), New York, NY, USA. Electronic address: chm2042@med.cornell.edu.
3
Department of Medicine and Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA. Electronic address: amm2014@med.cornell.edu.

Abstract

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.

PMID:
27162099
PMCID:
PMC4903929
DOI:
10.1016/j.gde.2016.03.011
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center