TY - JOUR
T1 - MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
AU - Huntly, Brian J.P.
AU - Shigematsu, Hirokazu
AU - Deguchi, Kenji
AU - Lee, Benjamin H.
AU - Mizuno, Shinichi
AU - Duclos, Nicky
AU - Rowan, Rebecca
AU - Amaral, Sonia
AU - Curley, David
AU - Williams, Ifor R.
AU - Akashi, Koichi
AU - Gilliland, D. Gary
N1 - Funding Information:
We acknowledge the members of the Gilliland and Akashi labs for helpful discussion. This work was supported by NIH grants CA66996 and DK50654, and a Leukemia and Lymphoma Society Center grant. (D.G.G.). D.G.G. is an Investigator of the Howard Hughes Medical Institute and is a Doris Duke Distinguished Clinical Scientist. B.J.P.H is a Senior Clinical Fellow of the Leukemia Research Fund (UK).
PY - 2004/12
Y1 - 2004/12
N2 - To better understand the origin of leukemic stem cells, we tested the hypothesis that all leukemia oncogenes could transform committed myeloid progenitor cells lacking the capacity for self-renewal, as has recently been reported for MLL-ENL. Flow-sorted populations of common myeloid progenitors and granulocyte-monocyte progenitors were transduced with the oncogenes MOZ-TIF2 and BCR-ABL, respectively. MOZ-TIF2-transduced progenitors could be serially replated in methylcellulose cultures and continuously propagated in liquid culture, and resulted in an acute myeloid leukemia in vivo that could be serially transplanted. In contrast, BCR-ABL transduction conferred none of these properties to hematopoietic progenitors. These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death.
AB - To better understand the origin of leukemic stem cells, we tested the hypothesis that all leukemia oncogenes could transform committed myeloid progenitor cells lacking the capacity for self-renewal, as has recently been reported for MLL-ENL. Flow-sorted populations of common myeloid progenitors and granulocyte-monocyte progenitors were transduced with the oncogenes MOZ-TIF2 and BCR-ABL, respectively. MOZ-TIF2-transduced progenitors could be serially replated in methylcellulose cultures and continuously propagated in liquid culture, and resulted in an acute myeloid leukemia in vivo that could be serially transplanted. In contrast, BCR-ABL transduction conferred none of these properties to hematopoietic progenitors. These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death.
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U2 - 10.1016/j.ccr.2004.10.015
DO - 10.1016/j.ccr.2004.10.015
M3 - Article
C2 - 15607963
AN - SCOPUS:19944385935
SN - 1535-6108
VL - 6
SP - 587
EP - 596
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -
