Functional Heterogeneity of Genetically Defined Subclones in Acute Myeloid Leukemia.
Cancer Cell, March 2014
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, Klco JM, Spencer DH, Miller CA, Griffith M, Lamprecht TL, O'Laughlin M, Fronick C, Magrini V, Demeter RT, Fulton RS, Eades WC, Link DC, Graubert TA, Walter MJ, Mardis ER, Dipersio JF, Wilson RK, Ley TJ
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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