Activation of mTORC1 signaling pathway in AIDS-related lymphomas.
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.
El-Salem
Mouna
M
University of Pennsylvania Medical Center, Department of Pathology and Laboratory Medicine, 3400 Spruce Street, 7.106 Founders Pavilion, Philadelphia, PA 19104, USA.
Raghunath
Puthiyaveettil N
PN
Marzec
Michal
M
Liu
Xiaobin
X
Kasprzycka
Monika
M
Robertson
Erle
E
Wasik
Mariusz A
MA
D045163:Antibodies, Phospho-Specific / Q000276:immunology; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000378:metabolism* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D010768:Phosphoserine / Q000032:analysis / Q000276:immunology; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology
D045163:Antibodies, Phospho-Specific; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D010768:Phosphoserine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases