Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II.
Hepatosplenic T cell lymphoma (HSTCL) is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant pr...
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doaj-7b03efe4b1a14809b9eb075c696fbe372020-11-25T02:15:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4941310.1371/journal.pone.0049413Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II.Weici ZhangMasanobu TsudaGuo-Xiang YangKoichi TsuneyamaXiao-Song HeAftab A AnsariWilliam M RidgwayRoss L CoppelZhe-Xiong LianPatrick S C LeungM Eric GershwinHepatosplenic T cell lymphoma (HSTCL) is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFβRII (dnTGFβRII) under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFβRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4(-)CD8(-)TCRβ(+)NK1.1(+) or CD8(+)TCRβ(+)NK1.1(-) T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2×10(4) isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFβRII is critical for development of lymphoma-like T cell infiltration.http://europepmc.org/articles/PMC3492285?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weici Zhang Masanobu Tsuda Guo-Xiang Yang Koichi Tsuneyama Xiao-Song He Aftab A Ansari William M Ridgway Ross L Coppel Zhe-Xiong Lian Patrick S C Leung M Eric Gershwin |
spellingShingle |
Weici Zhang Masanobu Tsuda Guo-Xiang Yang Koichi Tsuneyama Xiao-Song He Aftab A Ansari William M Ridgway Ross L Coppel Zhe-Xiong Lian Patrick S C Leung M Eric Gershwin Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. PLoS ONE |
author_facet |
Weici Zhang Masanobu Tsuda Guo-Xiang Yang Koichi Tsuneyama Xiao-Song He Aftab A Ansari William M Ridgway Ross L Coppel Zhe-Xiong Lian Patrick S C Leung M Eric Gershwin |
author_sort |
Weici Zhang |
title |
Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. |
title_short |
Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. |
title_full |
Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. |
title_fullStr |
Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. |
title_full_unstemmed |
Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II. |
title_sort |
lymphoma-like t cell infiltration in liver is associated with increased copy number of dominant negative form of tgfβ receptor ii. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Hepatosplenic T cell lymphoma (HSTCL) is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFβRII (dnTGFβRII) under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFβRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4(-)CD8(-)TCRβ(+)NK1.1(+) or CD8(+)TCRβ(+)NK1.1(-) T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2×10(4) isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFβRII is critical for development of lymphoma-like T cell infiltration. |
url |
http://europepmc.org/articles/PMC3492285?pdf=render |
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