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17 Publications visible to you, out of a total of 17
Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States.
MMML-MYC-SYS

Abstract (Expand)

Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, … which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12.

Authors: L. Hopp, H. Loffler-Wirth, H. Binder

Date Published: 7th Sep 2015

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

Association of NADPH oxidase polymorphisms with anthracycline-induced cardiotoxicity in the RICOVER-60 trial of patients with aggressive CD20(+) B-cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

AIM: To identify gene variants responsible for anthracycline-induced cardiotoxicity. PATIENTS & METHODS: Polymorphisms of the NADPH oxidase subunits and of the anthracycline transporters ABCC1, … ABCC2 and SLC28A3 were genotyped in elderly patients (61-80 years) treated for aggressive CD20(+) B-cell lymphomas with CHOP-14 with or without rituximab and followed up for 3 years. RESULTS: The accumulation of RAC2 subunit genotypes TA/AA among cases was statistically significant upon adjustment for gender, age and doxorubicin dose in a multivariate logistic regression analysis (OR: 2.3, p = 0.028; univariate: OR: 1.8, p = 0.077). RAC2 and CYBA genotypes were significantly associated with anthracycline-induced cardiotoxicity in a meta-analysis of this and a similar previous study. CONCLUSION: Our results support the theory that NADPH oxidase is involved in anthracycline-induced cardiotoxicity. Original submitted 9 July 2014; Revision submitted 19 December 2014.

Authors: A. Reichwagen, M. Ziepert, M. Kreuz, U. Godtel-Armbrust, T. Rixecker, V. Poeschel, M. Reza Toliat, P. Nurnberg, M. Tzvetkov, S. Deng, L. Trumper, G. Hasenfuss, M. Pfreundschuh, L. Wojnowski

Date Published: 1st Apr 2015

Publication Type: Not specified

Human Diseases: B-cell lymphoma

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin … Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with ECFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study.

Authors: N. Murawski, G. Held, M. Ziepert, B. Kempf, A. Viardot, M. Hanel, M. Witzens-Harig, R. Mahlberg, C. Rube, J. Fleckenstein, C. Zwick, B. Glass, N. Schmitz, S. Zeynalova, M. Pfreundschuh

Date Published: 31st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Elevated serum free light chains do not predict outcome of elderly patients with aggressive CD20(+) B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract

Not specified

Authors: M. Achenbach, J. T. Bittenbring, M. Ziepert, E. Regitz, G. Ott, A. Rosenwald, M. Pfreundschuh, B. Altmann, G. Held

Date Published: 1st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Portraying the Expression Landscapes of B-CellLymphoma-Intuitive Detection of Outlier Samples and of Molecular Subtypes.
MMML-MYC-SYS

Abstract (Expand)

We present an analytic framework based on Self-Organizing Map (SOM) machine learning to study large scale patient data sets. The potency of the approach is demonstrated in a case study using gene … expression data of more than 200 mature aggressive B-cell lymphoma patients. The method portrays each sample with individual resolution, characterizes the subtypes, disentangles the expression patterns into distinct modules, extracts their functional context using enrichment techniques and enables investigation of the similarity relations between the samples. The method also allows to detect and to correct outliers caused by contaminations. Based on our analysis, we propose a refined classification of B-cell Lymphoma into four molecular subtypes which are characterized by differential functional and clinical characteristics.

Authors: L. Hopp, K. Lembcke, H. Binder, H. Wirth

Date Published: 2nd Dec 2013

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

Impact of rituximab and radiotherapy on outcome of patients with aggressive B-cell lymphoma and skeletal involvement.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To study clinical presentation, outcome, and the role of radiotherapy in patients with aggressive B-cell lymphoma and skeletal involvement treated with and without rituximab. PATIENTS AND … METHODS: Outcome of patients with skeletal involvement was analyzed in a retrospective study of nine consecutive prospective trials of the German High-Grade Non-Hodgkin lymphoma Study Group. RESULTS: Of 3,840 patients, 292 (7.6%) had skeletal involvement. In the MabThera International Trial (MInT) for young good-prognosis patients and the Rituximab With CHOP Over 60 Years (RICOVER-60) study for elderly patients, the randomized addition of rituximab improved event-free survival (EFS; hazard ratio for MInT [HRMInT] = 0.4, P > 001; hazard ratio for RICOVER-60 [HRRICOVER-60] = 0.6, P > .001) and overall survival (OS; HRMInT = 0.4, P < .001; HRRICOVER-60 = 0.7, P = .002) in patients without skeletal involvement, but failed to improve the outcome of patients with skeletal involvement (EFS: HRMInT = 1.4, P = .444; HRRICOVER-60 = 0.8, P = .449; OS: HRMInT = 0.6, P = .449; HRRICOVER-60 = 1.0, P = .935). Skeletal involvement was associated with a worse outcome after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (HREFS = 1.5, P = .048; HROS = 1.1; P = .828), but not after CHOP without rituximab (HREFS = 0.8, P = .181; HROS = 0.7, P = .083). In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a decreased risk (HREFS = 0.3, P = .001; HROS = 0.5; P = .111). CONCLUSION: Rituximab failed to improve the outcome of patients with diffuse large B-cell lymphoma with skeletal involvement, although our data suggest a beneficial effect of radiotherapy to sites of skeletal involvement. Whether radiotherapy to sites of skeletal involvement can be spared in cases with a negative positron emission tomography after immunochemotherapy should be addressed in appropriately designed prospective trials.

Authors: G. Held, S. Zeynalova, N. Murawski, M. Ziepert, B. Kempf, A. Viardot, M. Dreyling, M. Hallek, M. Witzens-Harig, J. Fleckenstein, C. Rube, C. Zwick, B. Glass, N. Schmitz, M. Pfreundschuh

Date Published: 10th Nov 2013

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Comparison and modelling of pegylated or unpegylated G-CSF schedules in CHOP-14 regimen of elderly patients with aggressive B-cell lymphoma.
GLA - German Lymphoma Alliance, Genetical Statistics and Systems Biology

Abstract (Expand)

Bi-weekly (R)-CHOP therapy is one of the standard treatmentS for elderly patients with aggressive B-cell lymphoma, but it is only feasible with supportive G-CSF treatment. In the trials of the DSHNHL, … either unpegylated G-CSF was given daily over 7 or 10 days or pegylated G-CSF was applied at day 4 of each cycle. These schedules were planned on the basis of simulations of a biomathematical pharmacokinetic/pharmacodynamic model. By analysing the observed data, we investigated whether our model predictions were correct and whether even better schedules can be proposed. We used data on 249 matched patients of two prospective trials, RICOVER-60 and PEGFILGRASTIM. The three G-CSF-schedules showed similar outcomes regarding leukocytopenia, infections and days in hospital, with pegylated G-CSF having slightly but not significantly better scores in all three endpoints. Regarding pegylated G-CSF, the best timing is predicted to be any day between days 4 and 7. With respect to unpegylated G-CSF, the starting day is less important, but it should be continued until the end of each cycle.The three G-CSF-schedules are interchangeable in (R)-CHOP-14 for elderly patients with aggressive B-cell lymphoma. Our model correctly predicts time courses of leukocytes. Further model predictions are presented, which can be tested in subsequent clinical trials.

Authors: S. Zeynalova, M. Ziepert, M. Scholz, S. Schirm, C. Zwick, M. Pfreundschuh, M. Loeffler

Date Published: 30th Jul 2013

Publication Type: Not specified

Human Diseases: B-cell lymphoma

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