MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors.
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.
Huntly
Brian J P
BJ
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. bhuntly@rics.bwh.harvard.edu
Shigematsu
Hirokazu
H
Deguchi
Kenji
K
Lee
Benjamin H
BH
Mizuno
Shinichi
S
Duclos
Nicky
N
Rowan
Rebecca
R
Amaral
Sonia
S
Curley
David
D
Williams
Ifor R
IR
Akashi
Koichi
K
Gilliland
D Gary
DG
D000208:Acute Disease; D000818:Animals; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D016313:Genes, abl / Q000235:genetics / Q000502:physiology*; D042381:Granulocyte Precursor Cells / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007377:Interleukin-3 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009154:Mutation; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*
D007377:Interleukin-3; C475973:MOZ-TIF2 protein, human; D015514:Oncogene Proteins, Fusion