A5070860792- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Cancer Mechanisms and Therapy
- Signaling Pathways in Disease
- Advanced biosensing and bioanalysis techniques
- Blood disorders and treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Thermoelectric Materials and Devices
- Ocular Surface and Contact Lens
- Optical properties and cooling technologies in crystalline materials
- T-cell and B-cell Immunology
- Retinal Development and Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Drug Transport and Resistance Mechanisms
- Evolution and Genetic Dynamics
- Chemokine receptors and signaling
- Ocular Disorders and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
Universitätsklinikum Würzburg
2021-2025
University of Würzburg
2021-2024
Seoul National University
2022
Abstract The definition of high‐risk (HR) multiple myeloma (MM) is still a matter debate. We prospectively evaluated the HR detection using FISH in combination with SKY92 gene expression profiling 258 MM patients (newly diagnosed [ND] MM: n = 109; relapsed/refractory [RR] 149). was significantly enriched RRMM (57/121, 47.1%) compared NDMM (17/95, 17.9%) ( p < 0.0001). showed shorter progression‐free survival (PFS) 0.0001) and overall (OS) than standard‐risk (SR). In NDMM, also indicated...
Abstract Background: Even with considerable advancements in multiple myeloma (MM) therapy, proteasome inhibitors (PIs) continue to be an indispensable treatment pillar MM. However, the development of PI resistance remains a significant clinical challenge. Previous studies proposed different causes contributing PI-resistance, though, these mechanisms explain only subset cases. Hence, we employed multi-omics approach identify further molecular pathways underlying Methods: We applied proteomic...
Abstract Background: The treatment landscape in Multiple Myeloma (MM) shifts towards immunotherapies with the G protein-coupled receptor class C group 5 member D (GPRC5D) as a promising antigen for T cell engagers (TCE) and investigational CART constructs. Monoallelic genetic alterations GPRC5D are present up to 15% of MM patients prior directed therapy. incidence acquired biallelic events following has be determined. Recently, loss was identified underlying mechanism resistance toward...
For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed were only reported for minority resistant patients. The large complex machinery. Here, we focus on AAA ATPases 19S regulator (PSMC1-6) their implication in PI resistance. As an example cancer evolution acquisition resistance, conducted in-depth analysis index patient by applying FISH, WES,...
Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides unique therapeutic option patients ineligible CAR-T and bispecific antibody therapy, and/or progressing on anti-CD38 where bispecifics might be kept in reserve. Wider use drug can challenged by its distinct ocular side effect profile, including corneal microcysts keratopathy. While dose reduction has been most effective...
Summary Biomarkers for cytopenias following CAR T‐cell treatment in relapsed/refractory (RR) multiple myeloma (MM) are not completely defined. We prospectively analysed 275 sequential peripheral blood (PB) samples from 58 RRMM patients treated with BCMA‐targeted T cells, and then divided them into three groups: (i) baseline (before leukapheresis), (ii) ≤day+30, (iii) >day+30 after therapy. evaluated laboratory data performed flow cytometry to determine the (CAR) subsets. Baseline...
Abstract Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses one biggest clinical challenges. TP53 alterations are established high‐risk markers included in current staging criteria. KRAS most frequently mutated gene affecting around 20% MM patients. Applying Clonal Competition Assays (CCA) by co‐culturing color‐labeled modified cell models, we recently showed that mono‐ biallelic transmit fitness advantage to cells. Here, report similar dynamic for...
Abstract Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically genetically heterogeneous. Moreover, several conditions with phenotypes overlapping syndrome have been described. This makes molecular diagnosis deaf–blindness challenging. Here, we performed exome sequencing analysis on 7 Mexican 52 Iranian probands retinal degeneration impairment (without intellectual disability). Clinical assessment involved ophthalmological examination...
Optimal carfilzomib dosing is a matter of debate. We analyzed the inhibition profiles proteolytic proteasome subunits β5, β2 and β1 after low-dose (20/27 mg/m2) versus high-dose (≥36 in 103 pairs peripheral blood mononuclear cells from patients with relapsed/refractory (RR) multiple myeloma (MM). β5 activity was inhibited (median >50%) vivo by 20 mg/m2, whereas were co-inhibited only 36 56 respectively. Coinhibition (P=0.0001) (P=0.0005) differed significantly between carfilzomib....
Abstract The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine algorithms, resulting improved response rates. Nevertheless, patients continue relapse the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has reported mediate acute lymphoblastic leukemia, this mechanism yet...