A5048054782- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- MicroRNA in disease regulation
- Viral-associated cancers and disorders
- CNS Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Parasitic infections in humans and animals
- Phagocytosis and Immune Regulation
- Genomic variations and chromosomal abnormalities
- PI3K/AKT/mTOR signaling in cancer
- Galectins and Cancer Biology
- Glioma Diagnosis and Treatment
- Extracellular vesicles in disease
Universität Ulm
2014-2023
University Hospital Ulm
2012-2022
Universitätsklinikum des Saarlandes
2018
Heidelberg University
2006
Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 were enrolled in a safety expansion cohort. Extended analysis of all patients, including the effect minimal residual disease (MRD) negativity outcome, now reported. Patients Methods Overall, 158 or...
The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information critical to understanding its pathogenesis. Transcriptome analyses CLL and the main normal B cell subsets from human blood spleen revealed that immunoglobulin variable region (IgV) gene unmutated derives mature CD5+ cells mutated a distinct, previously unrecognized CD5+CD27+ post–germinal center subset. Stereotyped V rearrangements are enriched among cells, providing independent evidence for...
Immunoglobulin heavy chain variable-region (VH) gene mutation status and zeta-associated protein 70 (ZAP-70) expression are correlated in chronic lymphocytic leukemia (CLL), but their concordance is variable. The goal of this study was to elucidate additional factors potentially characterizing discordance.We evaluated ZAP-70 by flow cytometry, VH DNA sequencing, genomic aberrations fluorescence situ hybridization 148 CLL patients. parameters were analyzed for associations individual...
To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 2, 16, 30), procarbazine (60 mg/m2 2–11) and lomustine (110 day 2)—R-MPL protocol. Owing to infectious complications, omitted during the study consecutive were treated R-MP Three cycles scheduled repeated on 43....
Abstract Epigenetic alterations, such as promoter hypermethylation, may drive cancer through tumor suppressor gene inactivation. However, we have limited ability to differentiate driver DNA methylation (DNAme) changes from passenger events. We developed DNAme inference–MethSig–accounting for the varying stochastic hypermethylation rate across genome and between samples. applied MethSig bisulfite sequencing data of chronic lymphocytic leukemia (CLL), multiple myeloma, ductal carcinoma in...
Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each a particular BcR IG. The largest subsets are #1, #2, #4 #8, associated specific clinicobiological characteristics outcomes in retrospective studies. We assessed the associations prognostic value these IG prospective multicenter clinical trials reflective two different situations: i) early-stage (watch-and-wait arm...
ObjectiveMeasuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint an intra-patient progression-free survival (PFS) ratio, defined as PFS interval associated with therapy (PFS2) divided by last prior systemic (PFS1), above 1.3 or, some studies, 1.33 or 1.5.MethodsTo investigate if concept ratios agreement actual response evaluations physicians, we conducted survey among members MASTER (Molecularly Aided Stratification...
Abstract Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified B cell malignancies. To address how NOTCH -mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) Mantle Cell Lymphoma (MCL), differing only their expression intracellular domain (ICD) or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape malignant by up-regulating PD-L1,...
In chronic lymphocytic leukemia (CLL), epigenetic alterations are considered to centrally shape the transcriptional signatures that drive disease evolution and underlie its biological clinical subsets. Characterizations of regulators, particularly histone-modifying enzymes, very rudimentary in CLL. efforts establish effectors CLL-associated oncogene T-cell 1A (TCL1A), we identified here lysine-specific histone demethylase KDM1A interact with TCL1A protein B-cells conjunction an increased...
Background: Patients suffering from hemolytic anemia, thrombocytopenia and organ damage may suffer microangiopathic anemia or also called thrombotic microangiopathy (TMA). This condition is caused by many different pathogenic mechanism always a life-threatening due to vessel occlusion in vital organs. Rapid careful workup mandatory identify the cause of TMA. To patients immune mediated thrombocytopenic purpura (iTTP) ADAMTS13 (a disintegrin metalloproteinase with thrombospondin type 1 motif,...
Inhibition of stromal cell PKC-β mitigates environment-mediated drug resistance in B malignancies.
Abstract Knowledge of the genomic landscape chronic lymphocytic leukemia (CLL) grows increasingly detailed, providing challenges in contextualizing accumulated information. To define underlying networks, we here perform a multi-platform molecular characterization. We identify major subgroups characterized by instability (GI) or activation epithelial-mesenchymal-transition (EMT)-like programs, which subdivide into non-inflammatory and inflammatory subtypes. GI CLL exhibit disruption genome...
Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs the germinal centre and allows B cells to change their primary DNA sequence diversify antigen receptors. Here, we report genome binding of Lamin B1, component nuclear envelope involved epigenetic chromatin regulation, reduced during B-cell activation formation lymphoid centres. Chromatin immunoprecipitation-Seq analysis showed kappa heavy variable immunoglobulin domains were released from B1 suppressive...