International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 148 - ANALYSIS OF THE HOMEOBOX GENE HEX AS AN ONCOGENE IN MURINE T CELL-DERIVED LYMPHOMAS

A George
Baylor College of Medicine

Justice, MJ
Baylor College of Medicine

Proviral insertions at the novel viral insertion site, Lvis1, occur frequently in B- and T-cell leukemias and lymphomas in AKXD mice and appear to activate two genes, the divergent homeobox gene Hex and the kinesin-related spindle protein gene mEg5, located near the Lvis1 locus. To determine whether Hex plays a role in the induction of lymphomas, we have generated transgenic mice ectopically expressing Hex in hematopoietic cells. We have also carried out transplants of bone marrow transduced with a Hex cDNA-carrying retrovirus into recipient mice to determine if transplanted cells undergo altered differentiation or transformation in vivo. Both transgenic and bone marrow transplant recipient mice develop hematologic neoplasias that have clonal rearrangements of the TCR locus and are Thy1+ and CD4+CD8+ or CD4-CD8-, indicating tumor origin from a precursor T-cell population. Proviral insertions in tumours in transplant mice are clonal and are transcriptionally active, indicating a causal role for Hex proviral insertions in the onset of neoplasia. Preliminary data also suggests that the overexpression of Hex in hematopoietic precursor cells inhibits contribution to mature blood cell lineages by these precursors. Our results indicate that Hex can act as an oncogene in the T cell lineage when overexpressed in precursor hematopoietic cells.


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