The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells.
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.
George
Alex
A
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Morse
Herbert C
HC
Justice
Monica J
MJ
D000818:Animals; D001854:Bone Marrow Cells / Q000821:virology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
C078492:HHEX protein, human; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens