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

ABSTRACT: Human ?? T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of ?? T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3(-/-)) developed ?? T-cell lymphoma that resembled human ?? 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(+), ?? T-cell receptor (TCR)(+), and ?? TCR(-), and expressed CD8(+)CD4(-), CD4(+)CD8(-), or a mixture of the two. Id3(-/-) ?? T-cell lymphoma used predominantly V?1.1, some V?3, yet no V?2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the ?? T-cell lymphoma into syngeneic Rag1(-/-) mice resulted in aggressive ?? T-cell lymphoma, identical to the Id3(-/-) donor. Thus, our data demonstrate that Id3 regulates the development of ?? T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human ?? T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human ?? T-cell lymphoma.

SUBMITTER: Li J 

PROVIDER: S-EPMC3031408 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature