The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic progenitor cells

Alternative pre‐mRNA splicing is emerging as a major control point in both the initiation and progression of tumourigenesis. Overexpression of the dominant negative Ikaros splice isoform, Ik6, is found in many human cancers particularly leukaemias. Ik6 has been demonstrated to have a role in cell su...

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Bibliographic Details
Published in:International journal of cancer 2008-09, Vol.123 (6), p.1240-1245
Main Authors: Ruiz, Anna, Williams, Owen, Brady, Hugh J.M.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blotting, Western
Cell Differentiation - physiology
Cell physiology
Cell Proliferation
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Flow Cytometry
Fundamental and applied biological sciences. Psychology
haematopoietic progenitor cell
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
ikaros
Ikaros Transcription Factor - genetics
Ikaros Transcription Factor - metabolism
immortalisation
Mice
Mice, Inbred C57BL
Molecular and cellular biology
Protein Isoforms - genetics
Protein Isoforms - metabolism
splice isoform
Transduction, Genetic
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Summary:Alternative pre‐mRNA splicing is emerging as a major control point in both the initiation and progression of tumourigenesis. Overexpression of the dominant negative Ikaros splice isoform, Ik6, is found in many human cancers particularly leukaemias. Ik6 has been demonstrated to have a role in cell survival in both myeloid‐ and lymphoid cytokine‐dependent cell lines. To investigate the oncogenic potential of Ik6, we retrovirally transduced murine haematopoietic progenitor cells with Ik6 and have analysed the effects on proliferation and differentiation of these precursors using myeloid and lymphoid in vitro colony formation assays. We found that Ik6 can immortalize haematopoietic progenitor cells in myeloid conditions. Using an in vivo transplantation assay, we found that Ik6 favours reconstitution by haematopoietic precursors. These findings suggest that Ik6 may play an important role in the generation of the leukaemic phenotype. © 2008 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.23706