Functional heterogeneity of genetically defined subclones in acute myeloid leukemia

Jeffery M. Klco, David H. Spencer, Christopher A. Miller, Malachi Griffith, Tamara L. Lamprecht, Michelle O'Laughlin, Catrina Fronick, Vincent Magrini, Ryan T. Demeter, Robert S. Fulton, William C. Eades, Daniel C. Link, Timothy A. Graubert, Matthew J. Walter, Elaine R. Mardis, John F. Dipersio, Richard K. Wilson, Timothy J. Ley

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

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.

Original languageEnglish
Pages (from-to)379-392
Number of pages14
JournalCancer Cell
Volume25
Issue number3
DOIs
StatePublished - Mar 17 2014

Fingerprint

Dive into the research topics of 'Functional heterogeneity of genetically defined subclones in acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this