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mTOR activity in AIDS-related diffuse large B-cell lymphoma.
Sara H Browne1, Julio A Diaz-Perez1, Michael Preziosi1
1Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA, United States of America.
Plos One
|February 14, 2017
Summary
The mTOR pathway is active in most AIDS-related diffuse large B-cell lymphomas (AR-DLBCL). Phosphorylated 70 ribosomal S6 protein-kinase (p70S6K) is a key indicator of this activity and may predict response to mTOR inhibitors.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Patients with HIV have an increased risk of non-Hodgkin lymphomas, even with HAART.
- Acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell lymphoma (AR-DLBCL) warrants further investigation into its molecular pathways.
- The mTOR pathway is a critical regulator of cell growth and proliferation.
Purpose of the Study:
- To investigate the activity of the mTOR pathway in AR-DLBCL.
- To examine the expression of phosphorylated 70 ribosomal S6 protein-kinase (p70S6K) and phosphorylated phosphatase and tensin homolog (pPTEN) in AR-DLBCL tissues.
- To correlate these markers with clinical and histopathologic features.
Main Methods:
- Immunohistochemistry was used to analyze p70S6K, pPTEN, and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40) expression in 126 AR-DLBCL tissue samples.
- Antibodies targeting specific epitopes of p70S6K (Ser235/236 and Ser240/244) were employed.
- Expression levels were assessed and correlated with clinical data.
Main Results:
- High levels of p70S6K were detected, particularly with the Ser240/244 epitope (86% positivity).
- p70S6K levels positively correlated with pPTEN expression (p = 0.016 and p = 0.007).
- pPRAS40 was highly expressed in 64.3% of cases, but showed no correlation with pPTEN or p70S6K.
Conclusions:
- The mTOR pathway is frequently active in AR-DLBCL.
- p70S6K expression, especially via the Ser240/244 epitope, serves as a reliable biomarker for mTOR pathway activation.
- p70S6K levels are independent of HIV viral load or CD4 counts, suggesting its utility in identifying patients who may benefit from mTOR inhibitors.
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