Mutation of inhibitory helix-loop-helix protein Id3 causes γδ T-cell lymphoma in mice

Jun Li, Takashi Maruyama, Pin Zhang, Joanne E. Konkel, Victoria Hoffman, Brian Zamarron, Wan Jun Chen

    Research output: Contribution to journalArticlepeer-review

    23 Citations (Scopus)

    Abstract

    Human γδ T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of γδ T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3-/-) developed γδ T-cell lymphoma that resembled human γδ T-cell lymphoma. The Id3-/- mice with lymphoma showed splenomegaly, hepatomegaly, and lymphadenopathy with involvement of bone marrow, thymus, kidney, and lungs between 6 and 15 months of age. Phenotypic analysis revealed that lymphomatous cells were cluster of differentiation (CD)3+, γδ T-cell receptor (TCR)+, and αβ TCR -, and expressed CD8+CD4-, CD4 +CD8-, or a mixture of the two. Id3-/- γδ T-cell lymphoma used predominantly Vγ1.1, some Vγ3, yet no Vγ2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the γδ T-cell lymphoma into syngeneic Rag1-/- mice resulted in aggressive γδ T-cell lymphoma, identical to the Id3-/- donor. Thus, our data demonstrate that Id3 regulates the development of γδ T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human γδ T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human γδ T-cell lymphoma.

    Original languageEnglish
    Pages (from-to)5615-5621
    Number of pages7
    JournalBlood
    Volume116
    Issue number25
    DOIs
    Publication statusPublished - 2010 Dec 16

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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