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.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Klco
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Spencer
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Miller
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Malachi
authors.initials: M
authors.lastname: Griffith
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lamprecht
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: O'Laughlin
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Catrina
authors.initials: C
authors.lastname: Fronick
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magrini
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demeter
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fulton
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Eades
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Graubert
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walter
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.affiliation: Division of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Dipersio
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: The 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.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
mesh_terms: D000818:Animals; D001483:Base Sequence; D060965:Clonal Evolution / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D016678:Genome / Q000235:genetics; D005838:Genotype; D064593:Heterografts; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D009368:Neoplasm Transplantation; D017422:Sequence Analysis, DNA