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The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells

Oncogene volume 22, pages 6764–6773 (2003)Cite this article

Abstract

Proviral insertions at the viral insertion site Lvis1 occur frequently in B- and T-cell leukemias and lymphomas in AKXD mice and activate two nearby genes, the divergent homeobox gene Hex and the kinesin-related spindle protein gene Eg5. To determine whether Hex misexpression results in the altered differentiation or neoplastic transformation of hematopoietic lineages, we have transplanted mice with bone marrow cells transduced with retrovirus containing the Hex coding region. High levels of Hex expression in hematopoietic precursor cells inhibit contribution to mature blood cell lineages by these precursors. Hex bone marrow transplant recipient mice also develop hematologic neoplasms that appear to originate in the bone marrow. The tumors have clonal rearrangements of the TCR locus, are Thy1+, and are CD4+CD8+, CD4−CD8−, or mixed, indicating tumor origin from a precursor T-cell population. Tumors in transplant mice contain clonal and transcriptionally active Hex proviral insertions, demonstrating a causal role for Hex misexpression in the onset of these neoplasms. Our results demonstrate that Hex can act as a T lineage oncogene when misexpressed in hematopoietic precursor cells.

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Acknowledgements

We thank Dr Robert Hawley for providing the MSCV-PGK-Hph construct, and Drs Warren Pear and Margaret Goodell for protocols and advice on bone marrow transduction and transplantation. We also thank Dr Clifford Bogue for providing Hex antiserum and for sharing results prior to publication. We wish to acknowledge Cammy Mason-Garrison for expert assistance with necropsies and other members of the Justice laboratory for technical assistance and valuable discussions. Finally, we thank Dr Jeffrey Rosen, Dr Sharon Plon, Dr Lawrence Donehower, Dr Margaret Goodell, and Dr John Belmont for advice and critical review of this manuscript. This work was supported by N.I.H. Public Health Service Grant CA63229 to MJJ.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Alex George & Monica J Justice

  2. MD/PhD Program, Baylor College of Medicine, Houston, TX, USA

    Alex George

  3. Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA

    Herbert C Morse III

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  1. Alex George
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Correspondence to Monica J Justice.

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George, A., Morse III, H. & Justice, M. The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells. Oncogene 22, 6764–6773 (2003). https://doi.org/10.1038/sj.onc.1206822

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