pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Epstein-Barr Virus (EBV) is linked to B-cell lymphomas, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear.
• Phosphorylated STAT3 (pSTAT3) expression is common in EBV-positive DLBCL and may drive oncogene expression like c-MYC.
• EBV might act as a cofactor for MYC dysregulation, potentially through the JAK1/STAT3 pathway.

Purpose of the Study:

• To investigate the association between EBV, pSTAT3, and MYC in EBV-positive DLBCL cases.
• To confirm EBV's involvement in activating the JAK1/STAT3 pathway and MYC deregulation.
• To identify the role of EBV in the JAK1/STAT3 pathway by examining pSTAT3 and its upstream protein, pJAK1.

Main Methods:

• Retrieved 51 DLBCL paraffin-embedded tissue samples from Malaysia.
• Used EBER-ISH to detect EBV expression in DLBCL tissues.
• Conducted immunohistochemistry for LMP1, pJAK1, pSTAT3, and MYC, and FISH for c-MYC gene rearrangement on ten EBV-positive DLBCL cases.

Main Results:

• Among ten EBV-positive DLBCL cases, 90% were non-GCB subtype and 88.9% expressed LMP1.
• pJAK1 expression was observed in 40% of EBV-positive DLBCL cases.
• 66.7% of EBV-positive DLBCL cases showed pSTAT3 positivity, indicating EBV's role in constitutive JAK/STAT pathway activation.

Conclusions:

• EBV positivity in DLBCL is associated with the non-GCB subtype and constitutive JAK/STAT pathway activation.
• 44.5% of EBV-positive DLBCL cases exhibited co-expression of pSTAT3 and MYC, but none had c-MYC gene rearrangement.
• Findings suggest EBV's role in non-GCB DLBCL lymphomagenesis and highlight the potential of targeting the pSTAT3-mediated pathway for therapy.