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 typ...

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Veröffentlicht in:The American journal of pathology 2009-08, Vol.175 (2), p.817-824
Hauptverfasser: El-Salem, Mouna, Raghunath, Puthiyaveettil N, Marzec, Michal, Liu, Xiaobin, Kasprzycka, Monika, Robertson, Erle, Wasik, Mariusz A
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container_issue 2
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container_title The American journal of pathology
container_volume 175
creator El-Salem, Mouna
Raghunath, Puthiyaveettil N
Marzec, Michal
Liu, Xiaobin
Kasprzycka, Monika
Robertson, Erle
Wasik, Mariusz A
description 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.
doi_str_mv 10.2353/ajpath.2009.080451
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subjects Antibodies, Phospho-Specific - immunology
Biological and medical sciences
Hematologic and hematopoietic diseases
Human viral diseases
Humans
Infectious diseases
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma, AIDS-Related - metabolism
Lymphoma, AIDS-Related - pathology
Mechanistic Target of Rapamycin Complex 1
Medical sciences
Multiprotein Complexes
Pathology
Phosphoserine - analysis
Phosphoserine - immunology
Proteins
Regular
TOR Serine-Threonine Kinases
Transcription Factors - analysis
Transcription Factors - biosynthesis
Transcription Factors - immunology
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
title Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas
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