Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II

Weici Zhang, Masanobu Tsuda, Guo Xiang Yang, Koichi Tsuneyama, Xiaosong He, Aftab A. Ansari, William M. Ridgway, Ross L. Coppel, Zhe Xiong Lian, Patrick S Leung, M. Eric Gershwin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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, 2×104 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.

Original languageEnglish (US)
Article numbere49413
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 7 2012

Fingerprint

T-cells
T-Cell Lymphoma
lymphoma
Infiltration
Liver
T-lymphocytes
liver
receptors
Peripheral T-Cell Lymphoma
Hepatomegaly
Adoptive Transfer
Splenomegaly
T-Lymphocyte Subsets
mice
Liver Diseases
Lymphoma
Spleen
Cell Count
splenomegaly
Transplants

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II. / Zhang, Weici; Tsuda, Masanobu; Yang, Guo Xiang; Tsuneyama, Koichi; He, Xiaosong; Ansari, Aftab A.; Ridgway, William M.; Coppel, Ross L.; Lian, Zhe Xiong; Leung, Patrick S; Gershwin, M. Eric.

In: PLoS One, Vol. 7, No. 11, e49413, 07.11.2012.

Research output: Contribution to journalArticle

Zhang, Weici ; Tsuda, Masanobu ; Yang, Guo Xiang ; Tsuneyama, Koichi ; He, Xiaosong ; Ansari, Aftab A. ; Ridgway, William M. ; Coppel, Ross L. ; Lian, Zhe Xiong ; Leung, Patrick S ; Gershwin, M. Eric. / Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II. In: PLoS One. 2012 ; Vol. 7, No. 11.
@article{4891aa3a0eda4520a75cecae62b014eb,
title = "Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II",
abstract = "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, 2×104 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.",
author = "Weici Zhang and Masanobu Tsuda and Yang, {Guo Xiang} and Koichi Tsuneyama and Xiaosong He and Ansari, {Aftab A.} and Ridgway, {William M.} and Coppel, {Ross L.} and Lian, {Zhe Xiong} and Leung, {Patrick S} and Gershwin, {M. Eric}",
year = "2012",
month = "11",
day = "7",
doi = "10.1371/journal.pone.0049413",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II

AU - Zhang, Weici

AU - Tsuda, Masanobu

AU - Yang, Guo Xiang

AU - Tsuneyama, Koichi

AU - He, Xiaosong

AU - Ansari, Aftab A.

AU - Ridgway, William M.

AU - Coppel, Ross L.

AU - Lian, Zhe Xiong

AU - Leung, Patrick S

AU - Gershwin, M. Eric

PY - 2012/11/7

Y1 - 2012/11/7

N2 - 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, 2×104 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.

AB - 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, 2×104 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.

UR - http://www.scopus.com/inward/record.url?scp=84868706920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868706920&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0049413

DO - 10.1371/journal.pone.0049413

M3 - Article

C2 - 23145171

AN - SCOPUS:84868706920

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e49413

ER -