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Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma
- Source :
- BioMed Research International, Vol 2018 (2018), BioMed Research International
- Publication Year :
- 2018
- Publisher :
- Hindawi, 2018.
-
Abstract
- 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.
- Subjects :
- Adult
Male
0301 basic medicine
Vincristine
Adolescent
Cyclophosphamide
Article Subject
lcsh:Medicine
General Biochemistry, Genetics and Molecular Biology
Young Adult
03 medical and health sciences
0302 clinical medicine
Bone Marrow
Recurrence
immune system diseases
hemic and lymphatic diseases
Biomarkers, Tumor
medicine
Humans
Bruton's tyrosine kinase
Child
B cell
Aged
Aged, 80 and over
General Immunology and Microbiology
biology
business.industry
lcsh:R
General Medicine
Middle Aged
medicine.disease
Neoplasm Proteins
Lymphoma
030104 developmental biology
medicine.anatomical_structure
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Rituximab
Lymphoma, Large B-Cell, Diffuse
Bone marrow
Neoplasm Recurrence, Local
business
Diffuse large B-cell lymphoma
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 23146133
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....67f6c0245fdda5fdf2031b26b90e89c6
- Full Text :
- https://doi.org/10.1155/2018/1042597