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Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation
- Publication Year :
- 2007
- Publisher :
- American Association of Cancer Research:150 South Independence Mall West, #826:Philadelphia, PA 19106:(215)440-9300, EMAIL: pubs@aacr.org, INTERNET: http://www.aacr.org, Fax: (215)440-7228, 2007.
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Abstract
- Angioimmunoblastic lymphoma (AILT) is the second most common subtype of peripheral T-cell lymphoma (PTCL) and is characterized by dismal prognosis. Thus far, only a few studies have dealt with its molecular pathogenesis. We performed gene expression profile (GEP) analysis of six AILT, six anaplastic large cell lymphomas (ALCL), 28 PTCL-unspecified (PTCL/U), and 20 samples of normal T lymphocytes (including CD4+, CD8+, and activated and resting subpopulations), aiming to (a) assess the relationship of AILT with other PTCLs, (b) establish the relationship between AILT and normal T-cell subsets, and (c) recognize the cellular programs deregulated in AILT possibly looking for novel potential therapeutic targets. First, we found that AILT and other PTCLs have rather similar GEP, possibly sharing common oncogenic pathways. Second, we found that AILTs are closer to activated CD4+, rather than to resting or CD8+ lymphocytes. Furthermore, we found that the molecular signature of follicular T helper cells was significantly overexpressed in AILT, reinforcing the idea that AILT may arise from such cellular counterpart. Finally, we identified several genes deregulated in AILT, including PDGFRA, REL, and VEGF. The expression of several molecules was then studied by immunohistochemistry on tissue microarrays containing 45 independent AILT cases. Notably, we found that the vascular endothelial growth factor (VEGF) was expressed not only by reactive cells, but also by neoplastic cells, and that nuclear factor-κB (NF-κB) activation is uncommon in AILT, as suggested by frequent exclusively cytoplasmic c-REL localization. Our study provides new relevant information on AILT biology and new candidates for possible therapeutic targets such as PDGFRA (platelet-derived growth factor α) and VEGF. [Cancer Res 2007;67(22):10703–10]
- Subjects :
- CD4-Positive T-Lymphocytes
Vascular Endothelial Growth Factor A
Cancer Research
Angioimmunoblastic T-cell lymphoma
Lymphoma
DISORDERS
T-Lymphocytes
medicine.medical_treatment
NF-KAPPA-B
NEOPLASTIC-CELLS
PROGRESSION
PDGFRA
CD8-Positive T-Lymphocytes
Biology
PROFILE
LYMPHADENOPATHY
Follicular cell
CLASSIFICATION
chemistry.chemical_compound
medicine
gene expression profiling
Humans
THALIDOMIDE
SIGNATURES
Oligonucleotide Array Sequence Analysis
lynphoma
Gene Expression Profiling
Growth factor
microarray
NF-kappa B
INHIBITOR
Lymphoma, T-Cell, Peripheral
T-Lymphocytes, Helper-Inducer
medicine.disease
Immunohistochemistry
Proto-Oncogene Proteins c-rel
Gene Expression Regulation, Neoplastic
Gene expression profiling
Vascular endothelial growth factor
Oncology
chemistry
Immune System
Immunology
Cancer research
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....24952e56949ff824f90aaa0b4fddc845