@article{7e6cbc5e49b54daba9ef48d5ddbb7cb8,
title = "Functional heterogeneity of genetically defined subclones in acute myeloid leukemia",
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.",
author = "Klco, {Jeffery M.} and Spencer, {David H.} and Miller, {Christopher A.} and Malachi Griffith and Lamprecht, {Tamara L.} and Michelle O'Laughlin and Catrina Fronick and Vincent Magrini and Demeter, {Ryan T.} and Fulton, {Robert S.} and Eades, {William C.} and Link, {Daniel C.} and Graubert, {Timothy A.} and Walter, {Matthew J.} and Mardis, {Elaine R.} and Dipersio, {John F.} and Wilson, {Richard K.} and Ley, {Timothy J.}",
note = "Funding Information: This work was supported by grants to J.M.K. (K08HL116605), T.J.L. from the National Cancer Institute (P01CA101937 and RO1CA162086) and the Barnes Jewish Hospital Foundation (00335-0505-02), and R.K.W. from the National Human Genome Research Institute (U54 HG003079). Technical assistance was provided by the Alvin J. Siteman Cancer Center Tissue Procurement Core, the High Speed Cell Sorting Core, and the Molecular and Genomic Analysis Core at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, which are all supported by the National Cancer Institute Cancer Center Support Grant P30CA91842. The authors also thank Mieke Hooke for invaluable animal husbandry, Sharon Heath for clinical annotation, Julie Ritchey and Dan George for technical assistance, and David Russler-Germain for critical reading of the manuscript. ",
year = "2014",
month = mar,
day = "17",
doi = "10.1016/j.ccr.2014.01.031",
language = "English",
volume = "25",
pages = "379--392",
journal = "Cancer Cell",
issn = "1535-6108",
number = "3",
}