A5091036159- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Chemokine receptors and signaling
- Genomics and Phylogenetic Studies
- Protist diversity and phylogeny
- Chronic Lymphocytic Leukemia Research
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Microbial Community Ecology and Physiology
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Transplantation: Methods and Outcomes
- Chromosomal and Genetic Variations
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Microbial Fuel Cells and Bioremediation
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
University of Ostrava
2019-2025
University Hospital Ostrava
2020-2025
Erasmus MC
2023
Primary plasma cell leukemia (PCL) is the most aggressive monoclonal gammopathy. It was formerly characterized by ≥ 20% circulating cells (CTCs) until 2021, when this threshold decreased to 5%. We hypothesized that primary PCL not a separate clinical entity, but rather it represents ultra-high-risk multiple myeloma (MM) elevated CTC levels.We assessed levels of CTCs multiparameter flow cytometry in 395 patients with newly diagnosed transplant-ineligible MM establish cutoff for identifies...
Abstract Extramedullary multiple myeloma (EMM) is an aggressive form of (MM). This study represents the most comprehensive next-generation sequencing analysis EMM tumors ( N = 14) to date, uncovering key molecular features and describing tumor microenvironment. We observed co-occurrence 1q21 gain/amplification MAPK pathway mutations in 79% samples, suggesting that these are crucial mutational events development. also demonstrated patients with mutated KRAS at time diagnosis have a...
Abstract PhyloFisher is a software package written primarily in Python3 that can be used for the creation, analysis, and visualization of phylogenomic datasets consist protein sequences from eukaryotic organisms. Unlike many existing pipelines, comes with manually curated database 240 protein‐coding genes, subset previous phylogenetic dataset sampled 304 taxa. The also utilize user‐created proteins, which may more appropriate shallow evolutionary questions. equipped set utilities to aid...
Abstract The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates these organelles are not absolutely essential to eukaryotic cells. However, degree which metabolism and cellular systems of this organism have adapted loss is unknown. Here, we report an extensive analysis M. genome address question. Unexpectedly, find structure content similar in complexity other eukaryotes less “reduced” than genomes some protists from Metamonada group it belongs....
Abstract Purpose: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor (CTC), adding immune biomarkers peripheral blood (PB) the identification of patients at progression due lost surveillance, could improve International Myeloma Working Group 20/2/20 model. Experimental Design: report outcomes 150 with SMM enrolled iMMunocell...
During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB independent of stimulation, which leads to development B-cell malignancies. However, exact molecular mechanisms downstream targets remain unresolved. We...
Summary Induction therapy followed by CD34 + cell mobilisation and autologous transplantation represents standard of care for multiple myeloma (MM). However, the anti‐CD38 monoclonal antibodies daratumumab isatuximab have been associated with impairment, yet mechanism remains unclear. In this study, we investigated effect three different regimens (dara‐VCd, isa‐KRd VTd) on cells using flow cytometry transcriptomics. Decreased peak concentration yields, longer collection delayed engraftment...
Abstract Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and survival, while amount of intracellular has strong predictive effect. Focused CRISPR screen, transcriptional proteomic analysis identify deubiquitinase OTUD1 as critical mediator synthesis, proteasome inhibitor sensitivity tumor...
Abstract Mitochondria of diverse eukaryotes have evolved various departures from the standard genetic code, but breadth possible modifications and their phylogenetic distribution are known only incompletely. Furthermore, it is that some codon reassignments in previously sequenced mitogenomes been missed, resulting inaccurate protein sequences databases. Here we show, considering codons at conserved amino acid positions mitogenome-encoded proteins, mitochondria green algal order...
ABSTRACT Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression‐free survival (PFS) overall (OS). Recently, MRD negativity was approved as an early clinical endpoint accelerated drug approval MM. Nevertheless, there limited evidence utility real‐world setting. In this retrospective multicenter study, we report outcomes 331 newly diagnosed MM patients with evaluation at Day+100 after autologous stem cell...
OTUD1 is a deubiquitinating enzyme involved in many cellular processes including cancer and innate, immune signaling pathways. Here, we perform proximity labeling-based interactome study that identifies largely present the translation RNA metabolism protein complexes. Biochemical analysis validates association with ribosome subunits, elongation factors E3 ubiquitin ligase ZNF598 but not initiation machinery. catalytic activity suppresses polyA triggered stalling through inhibition of...
Mitochondrial translation often exhibits departures from the standard genetic code, but full spectrum of these changes has certainly not yet been described and molecular mechanisms behind in codon meaning are rarely studied. Here we report a detailed analysis mitochondrial code stramenopile group Labyrinthulea (Labyrinthulomycetes) their relatives. In genus Aplanochytrium, UAG is termination encodes tyrosine, contrast to unaffected UAA codon. This change evolutionarily independent...
The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into role in immunity, focusing cell-B conjugate formation and activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes Jurkat cells, identified BAP1 as key positive regulator formation. Subsequent investigations knockout cells revealed impaired activation, evidenced decreased MAPK NF-kB...