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42 Publications visible to you, out of a total of 42
MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

MicroRNAs (miRNA, miR) are negative regulators of gene expression that play an important role in diverse biological processes such as development, cell growth, apoptosis and haematopoiesis, suggesting … their association with cancer. Here we analysed the expression signatures of 157 miRNAs in 58 diffuse large B-cell lymphoma (DLBCL), 46 follicular lymphoma (FL) and seven non-neoplastic lymph nodes (LN). Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145). As compared to LN, some miRNAs are differentially regulated in both lymphoma types (MIRN155, MIRN210, MIRN106A, MIRN149 and MIRN139). Conversely, some miRNAs show lymphoma-specific aberrant expression, such as MIRN9/9*, MIRN301, MIRN338 and MIRN213 in FL and MIRN150, MIRN17-5P, MIRN145, MIRN328 and others in DLBCL. A classification tree was computed using four miRNAs (MIRN330, MIRN17-5P, MIRN106a and MIRN210) to correctly identify 98% of all 111 cases that were analysed in this study. Finally, eight miRNAs were found to correlate with event-free and overall survival in DLBCL including known tumour suppressors (MIRN21, MIRN127 and MIRN34a) and oncogenes (MIRN195 and MIRNLET7G).

Authors: A. Roehle, K. P. Hoefig, D. Repsilber, C. Thorns, M. Ziepert, K. O. Wesche, M. Thiere, M. Loeffler, W. Klapper, M. Pfreundschuh, A. Matolcsy, H. W. Bernd, L. Reiniger, H. Merz, A. C. Feller

Date Published: 10th Jun 2008

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study … is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

Authors: K. Hohloch, S. Zeynalova, B. Chapuy, M. Pfreundschuh, M. Loeffler, M. Ziepert, A. C. Feller, L. Trumper, D. Hasenclever, G. Wulf, N. Schmitz

Date Published: 12th May 2016

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
GLA - German Lymphoma Alliance

Abstract (Expand)

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined … activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

Authors: B. Chapuy, C. Stewart, A. J. Dunford, J. Kim, A. Kamburov, R. A. Redd, M. S. Lawrence, M. G. M. Roemer, A. J. Li, M. Ziepert, A. M. Staiger, J. A. Wala, M. D. Ducar, I. Leshchiner, E. Rheinbay, A. Taylor-Weiner, C. A. Coughlin, J. M. Hess, C. S. Pedamallu, D. Livitz, D. Rosebrock, M. Rosenberg, A. A. Tracy, H. Horn, P. van Hummelen, A. L. Feldman, B. K. Link, A. J. Novak, J. R. Cerhan, T. M. Habermann, R. Siebert, A. Rosenwald, A. R. Thorner, M. L. Meyerson, T. R. Golub, R. Beroukhim, G. G. Wulf, G. Ott, S. J. Rodig, S. Monti, D. S. Neuberg, M. Loeffler, M. Pfreundschuh, L. Trumper, G. Getz, M. A. Shipp

Date Published: 2nd May 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

MYC rearrangements occur in 5% to 10% of diffuse large B-cell lymphomas (DLBCL) and confer an increased risk to cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) and rituximab … (R)-CHOP treated patients. We investigated the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression in a prospective randomized trial. Paraffin-embedded tumor samples from 442 de novo DLBCL treated within the RICOVER study of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry and fluorescence in situ hybridization (FISH) to detect protein expression and breaks of MYC, BCL2, and BCL6. Rearrangements of MYC, BCL2, and BCL6 were detected in 8.8%, 13.5%, and 28.7%, respectively. Protein overexpression of MYC (>40%) was encountered in 31.8% of tumors; 79.6% and 82.8% of tumors expressed BCL2 and BCL6, respectively. MYC translocations, MYChigh, BCL2high, and BCL6low protein expressions were associated with inferior survival. In multivariate Cox regression modeling, protein expression patterns of MYC, BCL2 and BCL6, and MYC rearrangements were predictive of outcome and provided prognostic information independent of the International Prognostic Index (IPI) for overall survival and event-free survival. A combined immunohistochemical or FISH/immunohistochemical score predicts outcome in DLBCL patients independent of the IPI and identifies a subset of 15% of patients with dismal prognosis in the high-risk IPI group following treatment with R-CHOP. Registered at http://www.cancer.gov/clinicaltrials: RICOVER trial of the DSHNHL is NCT 00052936.

Authors: H. Horn, M. Ziepert, C. Becher, T. F. Barth, H. W. Bernd, A. C. Feller, W. Klapper, M. Hummel, H. Stein, M. L. Hansmann, C. Schmelter, P. Moller, S. Cogliatti, M. Pfreundschuh, N. Schmitz, L. Trumper, R. Siebert, M. Loeffler, A. Rosenwald, G. Ott

Date Published: 21st Mar 2013

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

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