| First Author | Li J | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 25 | Pages | 5615-21 |
| PubMed ID | 20852128 | Mgi Jnum | J:167400 |
| Mgi Id | MGI:4868170 | Doi | 10.1182/blood-2010-03-274506 |
| Citation | Li J, et al. (2010) Mutation of inhibitory helix-loop-helix protein Id3 causes gammadelta T-cell lymphoma in mice. Blood 116(25):5615-21 |
| abstractText | Human gammadelta T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of gammadelta T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3(-/-)) developed gammadelta T-cell lymphoma that resembled human gammadelta 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(+), gammadelta T-cell receptor (TCR)(+), and alphabeta TCR(-), and expressed CD8(+)CD4(-), CD4(+)CD8(-), or a mixture of the two. Id3(-/-) gammadelta T-cell lymphoma used predominantly Vgamma1.1, some Vgamma3, yet no Vgamma2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the gammadelta T-cell lymphoma into syngeneic Rag1(-/-) mice resulted in aggressive gammadelta T-cell lymphoma, identical to the Id3(-/-) donor. Thus, our data demonstrate that Id3 regulates the development of gammadelta T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human gammadelta T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human gammadelta T-cell lymphoma. |
