NR4A1-mediated apoptosis suppresses lymphomagenesis and is associated with a favorable cancer-specific survival in patients with aggressive B-cell lymphomas.

Deutsch, Alexander J., Rinner, Beate, Wenzl, Kerstin, Pichler, Martin, Troppan, Katharina, Steinbauer, Elisabeth, Schwarzenbacher, Daniela, Reitter, Sonja, Feichtinger, Julia, Tierling, Sascha, Prokesch, Andreas, Scheideler, Marcel, Krogsdam, Anne, Thallinger, Gerhard G., Schaider, Helmut, Beham-Schmid, Christine and Neumeister, Peter (2014) NR4A1-mediated apoptosis suppresses lymphomagenesis and is associated with a favorable cancer-specific survival in patients with aggressive B-cell lymphomas.. Blood, 123 15: 2367-2377. doi:10.1182/blood-2013-08-518878


Author Deutsch, Alexander J.
Rinner, Beate
Wenzl, Kerstin
Pichler, Martin
Troppan, Katharina
Steinbauer, Elisabeth
Schwarzenbacher, Daniela
Reitter, Sonja
Feichtinger, Julia
Tierling, Sascha
Prokesch, Andreas
Scheideler, Marcel
Krogsdam, Anne
Thallinger, Gerhard G.
Schaider, Helmut
Beham-Schmid, Christine
Neumeister, Peter
Title NR4A1-mediated apoptosis suppresses lymphomagenesis and is associated with a favorable cancer-specific survival in patients with aggressive B-cell lymphomas.
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
0006-4971
Publication date 2014-04-10
Year available 2014
Sub-type Article (original research)
DOI 10.1182/blood-2013-08-518878
Open Access Status
Volume 123
Issue 15
Start page 2367
End page 2377
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2015
Language eng
Formatted abstract
NR4A1 (Nur77) and NR4A3 (Nor-1) function as tumor suppressor genes as demonstrated by the rapid development of acute myeloid leukemia in the NR4A1 and NR4A3 knockout mouse. The aim of our study was to investigate NR4A1 and NR4A3 expression and function in lymphoid malignancies. We found a vastly reduced expression of NR4A1 and NR4A3 in chronic lymphocytic B-cell leukemia (71%), in follicular lymphoma (FL, 70%), and in diffuse large B-cell lymphoma (DLBCL, 74%). In aggressive lymphomas (DLBCL and FL grade 3), low NR4A1 expression was significantly associated with a non–germinal center B-cell subtype and with poor overall survival. To investigate the function of NR4A1 in lymphomas, we overexpressed NR4A1 in several lymphoma cell lines. Overexpression of NR4A1 led to a higher proportion of lymphoma cells undergoing apoptosis. To test the tumor suppressor function of NR4A1 in vivo, the stable lentiviral-transduced SuDHL4 lymphoma cell line harboring an inducible NR4A1 construct was further investigated in xenografts. Induction of NR4A1 abrogated tumor growth in the NSG mice, in contrast to vector controls, which formed massive tumors. Our data suggest that NR4A1 has proapoptotic functions in aggressive lymphoma cells and define NR4A1 as a novel gene with tumor suppressor properties involved in lymphomagenesis.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 15 Jun 2014, 00:19:04 EST by System User on behalf of School of Medicine