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

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.

• Authors: 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
• Journal: Cancer cell (Cancer Cell) Vol. 6 Issue 6 Pg. 587-96 (Dec 2004) ISSN: 1535-6108 [Print] United States
• PMID: 15607963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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