Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma

Kreher, Stephan; Jöhrens, Korinna; Strehlow, Felicitas; Martus, Peter; Borowiec, Kathrin; Radke, Josefine; Heppner, Frank L.; Roth, Patrick; Thiel, Eckhard; Pietsch, Torsten; Weller, Michael; Korfel, Agnieszka

doi:10.1093/neuonc/nov046

Cited by 46 publications

(25 citation statements)

References 29 publications

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“…The present study is a retrospective study with a short follow-up time, and these limitations may explain the discrepancy between the present study and previous studies. Table III In the present study, no significant difference was observed between GCB and non-GCB subgroups on OS or PFS time, which is in accordance with earlier studies (12,17,18,24,30). These results may indicate that PCNSL has a common immunophenotype classification, but this subtype classification may not have an effect on prognosis.…”

Section: Analysis (Cox Test) ----------------------------------------supporting

confidence: 92%

“…Survival analyses revealed BCL-6 expression as an independent prognostic parameter of DLBCL associated with favorable outcomes, and its positivity indicates an improved disease course (21,29,45). The CALGB 50202 study of the prospective G-PCNSL-SG1 trial disclosed that BCL-6 may assume clinical relevance as an unfavorable prognostic biomarker in PCNSL (7,30). In the present study, BCL-6 expression was not associated with OS or PFS.…”

Section: Analysis (Cox Test) ----------------------------------------supporting

confidence: 41%

“…A number of previous studies (21,23,24,(28)(29)(30) have utilized immunohistochemical markers to predict the prognosis of PCNSL. However, the significance of immunohistochemical markers on the prognosis of PCNSL remains questionable due to limitations, including a small sample size, heterogeneous treatment regimens or different methods and standards of immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…BCL-6 may have an important role in regulating the differentiation of normal GCB cells, and its deregulated expression may contribute to lymphomagenesis (30). Previous studies about the prognostic significance of BCL-6 expression remain controversial.…”

Section: Analysis (Cox Test) ----------------------------------------mentioning

confidence: 99%

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Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

et al. 2017

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Abstract. The majority of primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphoma, characterized by poor prognosis. In the present study, the expression of cluster of differentiation (CD)10, B cell lymphoma (BCL)-6, multiple myeloma-1 (MUM-1), BCL-2, CD138 and Ki-67 was analyzed by immunohistochemistry in 89 Chinese PCNSL cases, and the potential prognostic significance was evaluated. CD10, BCL-6, MUM-1, BCL-2 and CD138 were positive in 16.9 (15/89), 51.7 (46/89), 92.1 (82/89), 73.3 (63/86) and 0% (0/65) of all cases, respectively. According to the Hans algorithm, 71 patients (79.8%) were classified into the non-germinal center B cell-like (non-GCB) group, indicating a post-germinal center origin of PCNSL. The median follow-up time of 73 patients was 13 months [95% confidence interval (CI), 10.93-15.08]. The median overall survival (OS) time was 45.3 months (95% CI, 25.01-65.59) and the median progression-free survival (PFS) time was 30.0 months (95% CI, 13.43-46.57). Age (>60 years) was associated with a shorter OS time (P=0.009). Ki-67 (cutoff point 90%) was associated with shorter OS (P=0.037) and shorter PFS (P=0.039) times. No other immunohistochemical markers were associated with prognosis. On multivariate analysis, age (>60 years) was associated with shorter OS time (P=0.038), but immunophenotype and expression status of Ki-67, CD10, BCL-6 and BCL-2 did not predict prognosis. In conclusion, high Ki-67 expression may predict poor prognosis in PCNSL. The present study was limited by its sample size and short follow-up time. This requires more evidence to further clinical study.

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Section: Analysis (Cox Test) ----------------------------------------supporting

confidence: 92%

Section: Analysis (Cox Test) ----------------------------------------supporting

confidence: 41%

Section: Discussionmentioning

confidence: 99%

Section: Analysis (Cox Test) ----------------------------------------mentioning

confidence: 99%

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Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

et al. 2017

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“…15 Immunohistochemical characterization of tumors from patients that participated in CALGB 50202 demonstrated that high BCL6 correlated with refractory disease and shorter progression-free and overall survival (Rubenstein et al, 2013b), thus representing a potentially useful molecular prognostic biomarker. While the adverse prognostic significance of high BCL-6 in PCNSL was recently confirmed in an independent large prospective trial, 24 several small retrospective studies provided a conflicting result - that BCL-6 correlates with a better prognosis . This discrepancy raises the possibility that the prognostic significance of BCL-6 may be dependent upon treatment-related factors, such as rituximab or whole-brain radiotherapy.…”

Section: Molecular Pathogenesis Of Pcnslmentioning

confidence: 99%

The Challenge of Primary Central Nervous System Lymphoma

Carnevale

Rubenstein

2016

Hematology/Oncology Clinics of North America

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Primary central nervous system lymphoma (PCNSL) represents one of the most challenging subtypes of aggressive non-Hodgkin’s lymphoma, not only with respect to establishing the diagnosis, but also with respect to therapeutic resistance and treatment-related complications. Emerging clinical data suggest that optimized outcomes are achieved with dose-intensive central nervous system (CNS)-penetrant chemotherapy and the avoidance of whole brain radiotherapy. There is also increasing evidence that anti-CD20 antibody-based immunotherapy, incorporated as a component of high-dose methotrexate-based induction programs, may also contribute to improved outcomes. One of the interesting clinical questions in the present era is the determination of the optimal consolidative approach in the management of patients after remission induction therapy, with high-dose chemotherapy, minus or plus autologous stem cell transplantion, as well as reduced-dose whole brain radiotherapy representing the dominant therapeutic options currently under investigation. Additionally, an accumulation of insights into the molecular and cellular basis of disease pathogenesis is providing a foundation for the generation of molecular tools to facilitate diagnosis as well as a roadmap for integration of targeted therapy within the developing therapeutic armamentarium for this challenging brain tumor.

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Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma

Shen

et al. 2022

Molecular Oncology

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To investigate the effect of Apatinib (an inhibitor targeting VEGFR-2) enhances chemosensitivity of ABT-199 on diffuse large B-cell lymphoma (DLBCL). Viability assay and flow cytometric assay for determining apoptosis, cell cycle, mitochondrial membrane potential, reactive oxygen species and immunoblotting were used to explore the combination effect in DLBCL cell lines, DLBCL patient samples, and DLBCL mouse models. RNA sequencing assay helped identify mechanisms of ABT-199 plus Apatinib. The results show that ABT-199 combined with Apatinib inhibited cell proliferation, reduced colony-forming capacity, and induced apoptosis and cell cycle arrest in DLBCL cells. Mechanistically, the combination therapy inhibited tumour cell growth and promoted tumour cell death by regulating EDN1 and MAPK-related pathways and activating the intrinsic apoptotic pathway. The effect of the combination therapy was also validated in primary DLBCL blasts and xenograft mouse models. Our findings indicate that Apatinib enhances the chemosensitivity of ABT-199 and might serve as a promising therapeutic strategy for DLBCL.

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Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma

Abstract: The findings are limited by the fact that only 23% of all G-PCNSL-SG1 patients could be included in the analysis. If validated in an independent cohort, BCL6 may assume clinical relevance as an unfavorable prognostic biomarker in PCNSL.

Cited by 46 publications

References 29 publications

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: Analysis of 89 cases

The Challenge of Primary Central Nervous System Lymphoma

Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma

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