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

doi:10.1016/j.ccr.2004.10.015

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

Cancer Cell. 2004 Dec;6(6):587-96. doi: 10.1016/j.ccr.2004.10.015.

Authors

Brian J P Huntly¹, 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

Affiliation

¹ Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. bhuntly@rics.bwh.harvard.edu

PMID: 15607963
DOI: 10.1016/j.ccr.2004.10.015

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Acute Disease
Animals
Blotting, Southern
Bone Marrow Cells / metabolism
Bone Marrow Cells / pathology
Cell Differentiation / genetics
Cell Lineage
Cell Proliferation / drug effects
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / pathology
Colony-Forming Units Assay
Flow Cytometry
Genes, abl / genetics
Genes, abl / physiology*
Granulocyte Precursor Cells / metabolism
Granulocyte Precursor Cells / pathology
Hematopoietic Stem Cells / metabolism
Hematopoietic Stem Cells / pathology*
Humans
Immunophenotyping
Interleukin-3 / pharmacology
Leukemia, Myeloid / genetics
Leukemia, Myeloid / pathology
Mice
Mice, Inbred C57BL
Models, Biological
Mutation
Myeloid Progenitor Cells / metabolism
Myeloid Progenitor Cells / pathology
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / physiology*

Substances

Interleukin-3
MOZ-TIF2 protein, human
Oncogene Proteins, Fusion

Abstract

Publication types

MeSH terms

Substances

Grants and funding