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Cancer Cell. 2014 Mar 17;25(3):379-92. doi: 10.1016/j.ccr.2014.01.031. Epub 2014 Mar 6.

Functional heterogeneity of genetically defined subclones in acute myeloid leukemia.

Author information

  • 1Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 2The Genome Institute, Washington University, St. Louis, MO 63110, USA.
  • 3Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 4The Genome Institute, Washington University, St. Louis, MO 63110, USA; Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: timley@wustl.edu.

Abstract

The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by whole-genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients.

Copyright © 2014 Elsevier Inc. All rights reserved.

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PMID:
24613412
[PubMed - indexed for MEDLINE]
PMCID:
PMC3983786
[Available on 2015/3/17]
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