Article

Activation of mTORC1 signaling pathway in AIDS-related lymphomas.

University of Pennsylvania Medical Center, Department of Pathology and Laboratory Medicine, 3400 Spruce Street, 7.106 Founders Pavilion, Philadelphia, PA 19104, USA.
American Journal Of Pathology (impact factor: 4.89). 09/2009; 175(2):817-24. DOI:10.2353/ajpath.2009.080451 pp.817-24
Source: PubMed

ABSTRACT Using immunohistochemistry with antibodies against the phosphoserine residues in both S6rp and 4E binding protein 1, we identified the activation of the mammalian target of rapamycin (mTORC)1 pathway in 29 cases of AIDS-related lymphoma. These cases represented a diverse spectrum of histological types of non-Hodgkin lymphoma (24 cases) and classic Hodgkin lymphoma (five cases). mTORC1 was also activated in the hyperplastic but not involuted follicles of HIV-associated lymphadenopathy in eight cases, supporting the notion that mTORC1 activation is a common feature of transformed lymphocytes irrespective of either their reactive or malignant phenotype. We also found that in B-cell lines that represent diffuse large B-cell lymphoma, Burkitt lymphoma, Epstein-Barr virus-infected lymphocytes, and human herpesvirus 8-positive primary effusion lymphoma, inhibitors of Syk, MEK, and, seemingly, phosphoinositide 3 kinases suppressed mTORC1 activation, in particular when these inhibitors were used in combination. These findings indicate that AIDS-related lymphoma and other histologically similar types of lymphomas that are derived from transformed B lymphocytes may display clinical responses to inhibitors that directly target mTORC1 or, possibly, upstream activators of the mTORC1 pathway.

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Keywords

4E binding protein 1
 
AIDS-related lymphoma
 
B lymphocytes
 
B-cell lines
 
Burkitt lymphoma
 
classic Hodgkin lymphoma
 
Epstein-Barr virus-infected lymphocytes
 
histologically similar types
 
HIV-associated lymphadenopathy
 
human herpesvirus 8-positive primary effusion lymphoma
 
involuted follicles
 
malignant phenotype
 
mammalian target
 
mTORC)1 pathway
 
mTORC1 activation
 
mTORC1 pathway
 
non-Hodgkin lymphoma
 
represent diffuse large B-cell lymphoma
 
target mTORC1
 
upstream activators