Expression of the Tpl2/Cot oncogene in human T-cell neoplasias.
BACKGROUND
Tpl2/Cot oncogene has been identified in murine T-cell lymphomas as a target of MoMuLV insertion. Animal and tissue culture studies have shown that Tpl2/Cot is involved in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production by T-cells contributing to T-cell proliferation. In the present report we examined a series of 12 adult patients with various T-cell malignancies, all with predominant leukemic expression in the periphery, for the expression of Tpl2/Cot oncogene in order to determine a possible involvement of Tpl2/Cot in the pathogenesis of these neoplasms.


RESULTS
Our results showed that Tpl2/Cot was overexpressed in all four patients with Large Granular Lymphocyte proliferative disorders (LGL-PDs) but in none of the remaining eight patients with other T-cell neoplasias. Interestingly, three of the LGL-PD patients displayed neutropenia, one in association with sarcoidosis. Serum TNF-alpha levels were increased in all Tpl2/Cot overexpressing patients while serum IL-2 was undetectable in all subjects studied. Genomic DNA analysis revealed no DNA amplification at the Tpl2/Cot locus in any of the samples analyzed.


CONCLUSIONS
We conclude that Tpl2/Cot, a gene extensively studied in animal and tissue culture T-cell models may be also involved in the development of human LGL-PD and may have a role in the pathogenesis of immune manifestations associated with these diseases. This is the first report implicating Tpl2/Cot in human T-cell neoplasias and provides a novel molecular event in the development of LGL-PDs.
Christoforidou
Anna V
AV
Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete and University Hospital of Heraklion, 71110 Heraklion, Crete, Greece. christoforidou@hotmail.com
Papadaki
Helen A
HA
Margioris
Andrew N
AN
Eliopoulos
George D
GD
Tsatsanis
Christos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D015458:Leukemia, T-Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008218:Lymphocytosis / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human