Bone Marrow Molecular Markers Associated with RelapsedRefractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

Abstract EN

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow.

Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis.

Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients.

Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry.

Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients.

The same smear could present positive expression of multiple proteins simultaneously.

Positive combinations of protein expression were associated with resistance.

The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs.

14%).

There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001).

Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears.

At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.