25 research outputs found
High CXCR4 expression impairs rituximab response and the prognosis of R-CHOP-treated diffuse large B-cell lymphoma patients
The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Data used to generate Figure 2. (XLSX 18 kb
High Expression of CXCR4 Impairs Anti-CD20 Monoclonal Antibody (Rituximab)-Dependent Cytotoxicity in Diffuse Large B-Cell Lymphoma
High Expression of CXCR4 Impairs Anti-CD20 Monoclonal Antibody (Rituximab)-Dependent Cytotoxicity in Diffuse Large B-Cell Lymphoma
Additional file 4: of The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Data used to generate Figure 3. (XLSX 16 kb
Additional file 4: of The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Data used to generate Figure 3. (XLSX 16 kb
Additional file 2: of The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Data used to generate Figure 1. (XLSX 26 kb
Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www.hemaclass.org. We expected that such a study could generate therapeutic information and a frame for future individual evaluation of molecular resistance detected at clinical relapse. CASE PRESENTATION: The patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III and treated with conventional R-CHOP [rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (P)]. Unfortunately, she suffered from severe toxicity but recovered during the following 6 months’ remission until biopsy-verified relapse. The patient refused second-line combination chemotherapy, but accepted 3 months’ palliation with R and chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present >9 years after primary diagnosis. Molecular studies and data evaluation by principal component analysis, mutation screening and copy number variations of the primary and relapsed tumor, identified a pattern of branched lymphoma evolution, most likely diverging from an in situ follicular lymphoma. Accordingly, the primary diagnosed transformed lymphoma was classified as a diffuse large B cell lymphoma (DLBCL) of the GCB/centrocytic subtype by “cell of origin BAGS” assignment and R sensitive and C, H, O and P resistant by “drug specific REGS” assignment. The relapsed DLBCL was classified as NC/memory subtype and R, C, H sensitive but O and P resistant. CONCLUSIONS: Thorough analysis of the tumor DNA and RNA documented a branched evolution of the two clinical diagnosed tFL, most likely transformed from an unknown in situ lymphoma. Classification of the malignant tissue for drug-specific resistance did not explain the unexpected long-term remission and potential cure. However, it is tempting to consider the anti-CD20 immunotherapy as the curative intervention in the two independent tumors of this case. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40164-016-0063-0) contains supplementary material, which is available to authorized users
Additional file 3: of The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Data used to generate Figure 2. (XLSX 18 kb
Additional file 1: of The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Systematic dose-response experiments for rituximab. The diffuse large B-cell lymphoma (DLBCL) cell lines RIVA and FARAGE were exposed to a two-fold serial dilution of the anti-CD20 antibody rituximab (15 different concentrations starting from 66.67 μg/mL) for 0 h and 48 h and, subsequently, incubated 2 h with the MTS-containing CellTiter 96® AQueous One Solution Reagent (Promega) before absorbance measurements at 492 nm. Thus, the center of MTS exposure was at 1 h and 49 h, respectively. Model-based pre-processing was performed using raw absorbance values obtained through these MTS-based experiments, and the G-model used to generate dose-response curves and obtain time-independent summary statistics, as previously described [27]. Dose-response experiments were repeated thrice for each cell line, using a minimum of three technical replicates per condition. (PDF 5 kb