Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma

Beachy, Sarah H., Onozawa, Masahiro, Chung, Yang Jo, Slape, Chris, Bilke, Sven, Francis, Princy, Pineda, Marbin, Walker, Robert L., Meltzer, Paul and Aplan, Peter D. (2012) Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma. Blood, 120 5: 1048-1059. doi:10.1182/blood-2012-01-401760


Author Beachy, Sarah H.
Onozawa, Masahiro
Chung, Yang Jo
Slape, Chris
Bilke, Sven
Francis, Princy
Pineda, Marbin
Walker, Robert L.
Meltzer, Paul
Aplan, Peter D.
Title Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2012-08-02
Year available 2012
Sub-type Article (original research)
DOI 10.1182/blood-2012-01-401760
Open Access Status Not yet assessed
Volume 120
Issue 5
Start page 1048
End page 1059
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
LIN28A and LIN28B, the mammalian homologs of lin-28, are implicated in malignant transformation in part because of their ability to promote degradation of the let-7 family of miRs. In the present study, we show that overexpression of Lin28b in vivo leads to an aggressive peripheral T-cell lymphoma (PTCL) characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells. Similar to patients with PTCL, Lin28b-transgenic mice show signs of inflammation such as eosinophilia, increased C-reactive protein, release of inflammatory cytokines, and pleural effusion. The PTCLs that develop in Lin28b mice are derived from activated T cells and show decreased let-7 expression, increased Il6 expression, activation of NF-κB, and infiltration of B cells, all resulting in an inflammatory microenvironment. In addition, LIN28B is overexpressed 7.5-fold in PTCL patient samples compared with activated CD4+ cells. The results of the present study demonstrate for the first time that Lin28b can transform primary cells in vivo, identify a previously unsuspected link between Lin28b and PTCL, and provide a unique animal model for the study of PTCL biology and therapy.
Keyword Cardiac & Cardiovascular Systems
Respiratory System
Surgery
Transplantation
Cardiovascular System & Cardiology
Respiratory System
Surgery
Transplantation
CARDIAC & CARDIOVASCULAR SYSTEMS
RESPIRATORY SYSTEM
TRANSPLANTATION
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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