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Published on: March 30, 2018
Phenotypic Characterization of Diffuse Large B-Cell Lymphoma Cells and Prognostic Impact
Julie Devin1, Alboukadel Kassambara1,2, Angélique Bruyer1
1CNRS UMR9002, Institute of Human Genetics, 34090 Montpellier, France.
Insights
Multiparameter flow cytometry (MFC) aids in diagnosing diffuse large B-cell lymphoma (DLBCL). A new risk score using BCL2, BCL6, CD11c, and LAIR1 gene expression predicts patient outcomes and treatment resistance.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Mature B-cell neoplasms, particularly diffuse large B-cell lymphoma (DLBCL), are common non-Hodgkin lymphomas.
- Multiparameter flow cytometry (MFC) offers a rapid and economical method for assessing lymphoid markers in these conditions.
Purpose of the Study:
- To establish a robust algorithm for DLBCL cell line authentication using MFC.
- To develop a gene expression-based risk score for predicting DLBCL patient outcomes.
- To explore the correlation between specific marker expression and treatment resistance in DLBCL.
Main Methods:
- MFC was used to characterize 27 lymphoid markers in 16 DLBCL cell lines.
- A risk score was developed based on the expression of BCL2, BCL6, CD11c, and LAIR1 genes in DLBCL samples.
- DLBCL cell line responses to cyclophosphamide, etoposide, doxorubicin, and gemcitabine were evaluated.
Main Results:
- A robust MFC algorithm for DLBCL cell line authentication was established.
- The gene expression-based risk score effectively stratified DLBCL patients into four risk groups.
- The risk score independently predicted overall survival and showed a correlation between BCL6 overexpression and etoposide resistance.
Conclusions:
- MFC is valuable for routine characterization of DLBCL cells and tumors for research and clinical purposes.
- The developed risk score offers a novel prognostic tool for DLBCL patients.
- Findings suggest potential links between specific marker expression and therapeutic response, guiding future treatment strategies.
Abstract:
Multiparameter flow cytometry (MFC) is a fast and cost-effective technique to evaluate the expression of many lymphoid markers in mature B-cell neoplasms, including diffuse large B cell lymphoma (DLBCL), which is the most frequent non-Hodgkin lymphoma. In this study, we first characterized by MFC the expression of 27 lymphoid markers in 16 DLBCL-derived cell lines to establish a robust algorithm for their authentication. Then, using the expression profile in DLBCL samples of the genes encoding B lymphoid markers that are routinely investigated by MFC, we built a gene expression-based risk score, based on the expression level of BCL2, BCL6, CD11c, and LAIR1, to predict the outcome of patients with DLBCL. This risk score allowed splitting patients in four risk groups, and was an independent predictor factor of overall survival when compared with the previously published prognostic factors. Lastly, to investigate the potential correlation between BCL2, BCL6, CD11c, and LAIR1 protein level and resistance to treatment, we investigated the response of the 16 DLBCL cell lines to cyclophosphamide, etoposide, doxorubicin, and gemcitabine. We found a correlation between BCL6 overexpression and resistance to etoposide. These results show the interest of MFC for the routine characterization of DLBCL cells and tumors samples for research and diagnostic/prognostic purposes.
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