Details

Autor(en) / Beteiligte

• Quek, Lynn
• Otto, Georg W
• Garnett, Catherine
• Lhermitte, Ludovic
• Karamitros, Dimitris
• Stoilova, Bilyana
• Lau, I-Jun
• Doondeea, Jessica
• Usukhbayar, Batchimeg
• Kennedy, Alison
• Metzner, Marlen
• Goardon, Nicolas
• Ivey, Adam
• Allen, Christopher
• Gale, Rosemary
• Davies, Benjamin
• Sternberg, Alexander
• Killick, Sally
• Hunter, Hannah
• Cahalin, Paul
• Price, Andrew
• Carr, Andrew
• Griffiths, Mike
• Virgo, Paul
• Mackinnon, Stephen
• Grimwade, David
• Freeman, Sylvie
• Russell, Nigel
• Craddock, Charles
• Mead, Adam
• Peniket, Andrew
• Porcher, Catherine
• Vyas, Paresh

Titel

Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage

Ist Teil von

• The Journal of experimental medicine, 2016-07, Vol.213 (8), p.1513-1535

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Our understanding of the perturbation of normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage expressing cell surface CD34. We show that in ∼25% of AML, with a distinct genetic mutation pattern where >98% of cells are CD34(-), there are multiple, nonhierarchically arranged CD34(+) and CD34(-) LSC populations. Within CD34(-) and CD34(+) LSC-containing populations, LSC frequencies are similar; there are shared clonal structures and near-identical transcriptional signatures. CD34(-) LSCs have disordered global transcription profiles, but these profiles are enriched for transcriptional signatures of normal CD34(-) mature granulocyte-macrophage precursors, downstream of progenitors. But unlike mature precursors, LSCs express multiple normal stem cell transcriptional regulators previously implicated in LSC function. This suggests a new refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genetic/epigenetic changes determines the disordered transcriptional program, resulting in LSC differentiation arrest at stages that are most like either progenitor or precursor stages of hemopoiesis.