MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors

Brian J.P. Huntly, Hirokazu Shigematsu, Kenji Deguchi, Benjamin H. Lee, Shinichi Mizuno, Nicky Duclos, Rebecca Rowan, Sonia Amaral, David Curley, Ifor R. Williams, Koichi Akashi, D. Gary Gilliland

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Abstract

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.

Original languageEnglish
Pages (from-to)587-596
Number of pages10
JournalCancer Cell
Volume6
Issue number6
DOIs
Publication statusPublished - Dec 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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    Huntly, B. J. P., Shigematsu, H., Deguchi, K., Lee, B. H., Mizuno, S., Duclos, N., Rowan, R., Amaral, S., Curley, D., Williams, I. R., Akashi, K., & Gilliland, D. G. (2004). MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell, 6(6), 587-596. https://doi.org/10.1016/j.ccr.2004.10.015