Functional Heterogeneity of Genetically Defined Subclones in Acute Myeloid Leukemia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2014 Mar 12

PMID 24613412

Citations 201

Authors

Jeffery M Klco

David H Spencer

Christopher A Miller

Malachi Griffith

Tamara L Lamprecht

Michelle OLaughlin

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

Affiliations

Soon will be listed here.

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.

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