Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a frequent non-Hodgkin's lymphoma subtype with high bone marrow infiltration.
• Over 30% of patients develop relapsed/refractory DLBCL post-first-line therapy, indicating a poor prognosis.

Purpose of the Study:

• To identify molecular markers in bone marrow aspirates for predicting relapsed/refractory ABC-DLBCL.
• To investigate the association between specific protein expressions and treatment resistance.

Main Methods:

• Bone marrow aspirate smears from 202 ABC-DLBCL patients were analyzed using immunocytochemistry.
• Expression levels of Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton's tyrosine kinase (BTK), and Bcl2 proteins were detected.

Main Results:

• Strong expression of Stat3, NF-κB p65, Syk, BTK, and Bcl2 was observed in ABC-DLBCL bone marrow smears.
• Simultaneous positive expression of multiple proteins correlated with drug resistance.
• The Stat3+/NF-κB+ group showed significantly higher resistance (80%) compared to the Stat3-/NF-κB- group (14%).
• Significant differences in two-year relapse-free survival were noted for combinations including Stat3-NF-κB, Bcl2-Stat3, Bcl2-Pax5, and BTK-Syk.

Conclusions:

• Key molecules in multiple signaling pathways were identified in bone marrow aspirates of ABC-DLBCL patients.
• These findings provide clinical evidence for drug-resistant molecules in ABC-DLBCL.
• The study offers a theoretical basis for developing rational second-line treatments for drug-resistant cases.