Karel Fišer

Karel Fišer
Charles University in Prague | CUNI · Department of Paediatric Haematology and Oncology (2. LF)

PhD.

About

78
Publications
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1,244
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Publications

Publications (78)
Article
Full-text available
Background The Human Cell Differentiation Molecules (HCDM) organizes Human Leukocyte Differentiation Antigen (HLDA) workshops to test and name clusters of antibodies that react with a specific antigen. These cluster of differentiation (CD) markers have provided the scientific community with validated antibody clones, consistent naming of targets an...
Article
Full-text available
We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March—October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and mult...
Article
Full-text available
Fusion of the ZNF384 gene as the 3' partner to several different 5' partner genes occurs recurrently in B-cell precursor acute lymphoblastic and mixed phenotype B/myeloid leukemia. These canonical fusions (ZNF384r) contain the complete ZNF384 coding sequence and are associated with a specific gene expression signature. Cases with this signature, bu...
Article
Full-text available
The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of tra...
Preprint
Full-text available
We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were...
Article
Full-text available
Background The immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known on the microenvironment of metastatic HGSCs and its potential influence on patient survival. Here, we explore the clinical relevance of the immunological configuration of HGSC metastases....
Article
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Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with early switch to the monocytic lineage and loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced switch detectable...
Article
Full-text available
ShinySOM offers a user-friendly interface for reproducible, high-throughput analysis of high-dimensional flow and mass cytometry data guided by self-organizing maps. The software implements a FlowSOM-style workflow, with improvements in performance, visualizations and data dissection possibilities. The outputs of the analysis include precise statis...
Article
Objective Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving. Rationale In this study, we sought to investigate the immunophenome of circulating human monocyte subs...
Article
Full-text available
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence spatially and temporally overlap and phenotypic markers are often shared, the specifics regarding their origin, development, lineage restriction and mutual relationships have not been fully determined. The identification of...
Conference Paper
CD molecules are surface molecules expressed on cells of the immune system that play key roles in immune cell-cell communication and sensing the microenvironment. These molecules are essential markers for the identification and isolation of leukocytes and lymphocyte subsets and their malignant counterparts. Here, we present the results of the first...
Article
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CD molecules are surface molecules expressed on cells of the immune system that play key roles in immune cell-cell communication and sensing the microenvironment. These molecules are essential markers for the identification and isolation of leukocytes and lymphocyte subsets. Here, we present the results of the first phase of the CD Maps study, mapp...
Article
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The emergence of cisplatin (CDDP) resistance is the main cause of treatment failure and death in patients with testicular germ cell tumors (TGCT), but its biologic background is poorly understood. To study the molecular basis of CDDP resistance in TGCT we prepared and sequenced CDDP-exposed TGCT cell lines as well as 31 primary patients’ samples. L...
Article
Full-text available
The organization of the nuclear periphery is crucial for many nuclear functions. Nuclear lamins form dense network at the nuclear periphery and play a substantial role in chromatin organization, transcription regulation and in organization of nuclear pore complexes (NPCs). Here, we show that TPR, the protein located preferentially within the nuclea...
Conference Paper
Full-text available
Background In 2014, we used flow‐cytometry (FC) to describe a subtype of pediatric B cell precursor acute lymphoblastic leukemia (BCP ALL) with a lineage switch of leukemic blasts into monocytoid cells (swALL) during early treatment (Slamova et al., 2014). Although part of the swALL cases harbored deletion of ERG (ERGdel) and/or IKZF1 alterations,...
Article
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Despite the wide application of nanomaterials, toxicity studies of nanoparticles (NP) are often limited to in vitro cell models, and the biological impact of NP exposure in mammals has not been thoroughly investigated. Zinc oxide (ZnO) NPs are commonly used in various consumer products. To evaluate the effects of the inhalation of ZnO NP in mice, w...
Article
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ERG-deletions occur recurrently in acute lymphoblastic leukemia, especially in the DUX4-rearranged subtype. The ERG-deletion was shown to positively impact prognosis of patients with IKZF1-deletion and its presence precludes assignment into IKZF1plus group, a novel high-risk category on AIEOP-BFM ALL trials. We analyzed the impact of different meth...
Article
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Novel biological subtypes and clinically important genetic aberrations (druggable lesions, prognostic factors) have been described in B-other acute lymphoblastic leukemia (ALL) during the last decade; however, due to a lack of studies on unselected cohorts, their population frequency and mutual associations still have to be established. We studied...
Preprint
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Efficient unbiased data analysis is a major challenge for laboratories handling large cytometry datasets. We present EmbedSOM, a non-linear embedding algorithm based on FlowSOM that improves the analyses by providing high-performance visualization of complex single cell distributions within cellular populations and their transition states. The algo...
Article
Introduction: Recently we described a subgroup of pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP ALL) with switching from B to monocytic lineage in early phase of the therapy (Slamova et al., 2014). In a limited cohort of patients with switching ALL (swALL), we observed inferior response to treatment with discrepancy of...
Article
The Flow Cytometry Standard (FCS) format is a widely accepted norm for storing Flow Cytometry (FCM) data. Its goal as a standard is to allow FCM data sharing and re‐analysis. Over more than three decades of its existence FCS has evolved into a well‐defined, flexible file format reflecting technical changes in the FCM field. Its flexibility as well...
Article
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene has distinct HOX gene signature in comparison to other subtypes...
Article
Full-text available
Burkholderia cenocepacia causes severe pulmonary infections in cystic fibrosis (CF) patients. Since the bacterium is virtually untreatable by antibiotics, chronic infections persist for years and might develop into fatal septic pneumonia (cepacia syndrome, CS). To devise new strategies to combat chronic B. cenocepacia infections, it is essential to...
Data
Structural variation of genes involved in metal metabolism. Genes undergoing parallel IS insertions and/or deletions are denoted by gray arrows. Novel IS insertions are marked with dots and their positions, orientations and types are indicated. Deleted regions are crossed out. Deletions and IS insertions were confirmed on assemblies of mapped seque...
Data
IS incidence in B. cenocepacia IIIA complete genomes. (XLSX)
Data
Nonsynonymous mutations within selected genes under parallel evolution in various B. cenocepacia IIIA longitudinal clonal lineages. Only mutations present in a subset of isolates of a particular RAPD type (i.e. that have arisen after the divergence of RAPD types) are denoted. The numbers in parentheses denote the percent of isolates from a particul...
Data
Whole-genome phylogeny of B. cenocepacia recA group IIIA genomes. Each MLST sequence type is represented with one genome (see S2 Table). Complete genomes are denoted in bold. The ST32/ST33 lineage and the epidemic ET12 lineage are indicated. The tree was constructed from 95,357 variant nucleotide positions using the CSIPhylogeny pipeline. (PDF)
Data
Summary information about 8 CS patients from whom the sequenced B. cenocepacia ST32 were isolated. (XLSX)
Data
Whole genome sequences of B. cenocepacia IIIA used for comparative genomic analyses. (DOCX)
Data
SNP distribution among B. cenocepacia ST32 genes. The grey columns denote total numbers of genes containing given numbers of nonsynonymous or synonymous SNPs among the ST32 WGS dataset (see Materials and Methods). Identical mutations (gyrA, katG) were counted separately if they arose independently in patient-specific lineages (as deduced from WGS p...
Data
Alignment of B. cenocepacia ST32 proteins and homologs with determined crystal structures. The mutated and catalytically important residues are colored as in Fig 4. Functional domains (DHp in CusS, βi4 in RpoB) are denoted with grey shading. (DOCX)
Data
LSDs in ST32 genomes sequenced in this study. Only regions of missing coverage larger than 10 kb are reported. (XLSX)
Data
Putative genomic islands in ST32 genome (GiST32). (XLSX)
Data
IS insertions in genomes of ST32 isolates sequenced in this study. (XLSX)
Data
Variant calling from mapping of WGS sequencing reads to the reference ST32 isolate 1232. Called variants with frequency ≥80%, coverage ≥15 and average quality ≥25 (only SNPs, not applied to other mutations) are reported. SNPs informative of within-patient evolution (see Materials and Methods) are listed in a separate sheet. (XLSX)
Data
List of primers used for PCR amplification of genes under parallel evolution. (DOCX)
Article
Full-text available
Hierarchical cluster analysis is a valuable tool for exploring data by describing their structure using a dendrogram. However, proper visualization and interactive inspection of the dendrogram are needed to unlock the information in the data. We describe a new R package, idendro, that enables the user to inspect dendrograms interactively: to select...
Article
Homeobox genes (HOX) encode transcription factors that are frequently deregulated in leukemias. Our previous results showed that HOX gene expression differs among genetically characterized subtypes of pediatric acute myeloid leukemia (AML). Specifically, PML-RARa positive AML patients have overall lowest HOX gene expression which positively correla...
Article
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To the editor: Mixed phenotype acute leukemias (MPALs) are a rare subset of acute leukemias that cannot be unambiguously assigned to a single hematopoietic lineage because of the significant expression of antigens from additional lineages. This subset comprises several entities, including
Article
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Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-b...
Article
Purpose: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). Methods: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF m...
Article
Full-text available
Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size excl...
Article
Differentiation during hematopoiesis leads to the generation of many cell types with specific functions. At various stages of maturation, the cells may change pathologically, leading to diseases including acute leukemias (ALs). Expression levels of regulatory molecules (such as the IKZF, GATA, HOX, FOX, NOTCH and CEBP families, as well as SPI-1/PU1...
Article
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The predictive strength of next-generation sequencing MRD detection for relapse compared with current methods in childhood ALL Minimal residual disease (MRD) monitoring via antigen receptor quantitative polymerase chain reaction (qPCR) is an important pre-dictor of outcome in childhood acute lymphoblastic leukemia (ALL), is rigorously standardized...
Article
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L-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategy will depend on the capacity of cancer cells to adapt to the metabolic challenge, which could rel...
Article
In a recent paper, McClellan et al. (1) report that blasts from some precursor B cell acute lymphoblastic leukemia (B-ALL) cases transdifferentiate (reprogram) into nonmalignant cells. Although showing induced reprogramming in both Philadelphia chromosome-positive (Ph+) and Ph− cases, the authors concentrate on Ph+ leukemias, proposing reprogrammin...
Article
Full-text available
Background Although distinct patterns of homeobox (HOX) gene expression have been described in defined cytogenetic and molecular subsets of patients with acute myeloid leukemia (AML), it is unknown whether these patterns are the direct result of transcriptional alterations or rather represent the differentiation stage of the leukemic cell.Method To...
Article
Introduction MRD is an important predictor of outcome in childhood ALL. Since 2000, MRD detected by quantitative PCR (qPCR) for immunoglobulin and T-cell receptor gene rearrangements with a minimal sensitivity of 1E-04 has been used for risk group stratification in pediatric BFM trials. Next generation sequencing (NGS) permits rapid parallel sequen...
Article
We identified a subset of BCP-ALL with switch towards the monocytic lineage within the first month of treatment (swALL)[Slámová et al Leukemia 2014]. During the switch cells gradually lose CD19 and CD34 expression and acquire CD33 and CD14 positivity. We proved clonal relatedness of switched monocytic blasts with the diagnostic leukemic cells based...
Article
Acute lymphoblastic leukemia (ALL) is the most frequent type of childhood cancer. The key component in the therapy, L-asparaginase (ASNase), hydrolyzes plasma asparagine and glutamine. Leukemic cells are sensitive to the depletion due to low activity of asparagine synthetase. Although the treatment is very effective, resistance and side effects rem...
Article
Homeobox genes (HOX) encode transcription factors that are frequently deregulated in leukemias. Our previous findings described that HOX gene expression differs among genetically characterized subtypes of pediatric AML with PML-RARa+ patients having the lowest overall HOX gene expression. We observed that HOX gene expression positively correlated w...
Article
Rationale: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. Objective: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patient...
Article
Full-text available
Switches from the lymphoid to myeloid lineage during B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment are considered rare and thus far have been detected in MLL-rearranged leukemia. Here, we describe a novel BCP-ALL subset, switching BCP-ALL or swALL, which demonstrated monocytosis early during treatment. Despite their monocytic ph...
Article
Leukemia is a complex disease pathologically manifested at the DNA, mRNA and protein level. Understanding leukemia pathogenesis is prevalently focused on mutations at the DNA (or mRNA) level, however the functional consequences of these changes on cellular machineries are not fully clarified. Since proteome analysis provides link between gene seque...
Article
CCAAT/enhancer binding protein alpha (CEBPα) is one of the crucial transcription factors involved in hematopoietic differentiation and leukemogenesis. CEBPα promotes myeloid differentiation by up-regulation of lineage specific genes and by cell proliferation arrest. Epigenetic regulation of CEBPα expression through DNA methylation has been demonstr...
Article
Introduction Homeobox (HOX) genes encode transcription factors crucial in embryogenesis. They are often dysregulated in malignancies including leukemias. The aberrant HOX gene expression and its regulation in leukemic cells is neither completely described nor understood. Aims Our main aim was to determine whether the leukemic HOX gene expression p...
Article
779 L-asparaginase (L-asp) is an important component of childhood acute lymphoblastic leukemia (ALL) therapy. Its cytotoxic effect is based on the depletion of extracellular asparagine and glutamine. Leukemic cells are sensitive to this depletion due to the lower activity of asparagine synthetase compared to healthy cells. However, the mechanism of...
Article
876 Immunophenotypic instability during early phase of ALL treatment is a frequent observation during flow cytometric minimal residual disease (FC MRD) monitoring. Antigens typically involved include CD10, CD20, CD34 and CD45 and these changes do not usually revoke initial disease classification and do not hamper FC MRD detection. We previously des...
Article
Full-text available
With the advent of primary PCI (PPCI), reperfusion is achieved in almost all patients presenting with acute myocardial infarction. However, despite multiple trials, reperfusion injury has not been successfully dealt with so far. In mouse models, CD4(+) T lymphocytes (T cells) have been shown to be crucial instigators of reperfusion injury. Our goal...
Article
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The combination of color-coded microspheres as carriers and flow cytometry as a detection platform provides new opportunities for multiplexed measurement of biomolecules. Here, we developed a software tool capable of automated gating of color-coded microspheres, automatic extraction of statistics from all subsets and validation, normalization, and...
Article
Full-text available
Flow cytometry is a valuable tool in research and diagnostics including minimal residual disease (MRD) monitoring of hematologic malignancies. However, its gradual advancement toward increasing numbers of fluorescent parameters leads to information rich datasets, which are challenging to analyze by standard gating and do not reflect the multidimens...
Article
Background: Primary PCI (PPCI) has substantially improved clinical outcomes of patients with acute ST elevation myocardial infarction (STEMI). However, myocardial ischemia-reperfusion (I/R) injury still remains an important clinical problem. CD4+ T-lymphocytes have been shown to promote I/R injury in a mouse model. It is unknown though, whether T-c...
Article
1708 Introduction Anecdotic observations of B precursor (BCP) ALL patients with aberrant CD2 expression at diagnosis and a significant shift of phenotype towards monocytes during induction treatment lead us to investigate the nature, incidence and characteristics of monocytic transdifferentiation. Patients and Design Patients with a significant s...
Article
Full-text available
The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at le...
Article
Flow cytometry is an important tool both for research and diagnostics of hematologic malignancies - including monitoring of minimal residual disease (MRD). Recent progress and more widespread availability of 6 and higher color flow cytometry leads to complex, information-rich datasets which are very challenging to analyze. Here, we validate a novel...