- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Hemoglobinopathies and Related Disorders
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Genomic variations and chromosomal abnormalities
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- MicroRNA in disease regulation
- Blood disorders and treatments
- HIV/AIDS drug development and treatment
- Sarcoma Diagnosis and Treatment
- Neutropenia and Cancer Infections
- Viral-associated cancers and disorders
- Hematopoietic Stem Cell Transplantation
- Mycobacterium research and diagnosis
Charles University
2016-2025
General University Hospital in Prague
2016-2025
National Cancer Center Hospital East
2023
Hudson Institute
2017
John Wiley & Sons (United States)
2017
Marien Hospital Düsseldorf
2016
Heinrich Heine University Düsseldorf
2016
Broad Institute
2004
Massachusetts Institute of Technology
2004
Dana-Farber Cancer Institute
2004
This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents.In total, 239 were randomly assigned (2:1) treatment (n = 160) placebo 79) once per day (on 28-day cycles). The primary end point was rate transfusion independence (TI)...
We report 17 cytopenic patients with myelodysplastic syndrome (MDS) of refractory anaemia (RA) subtype hyper‐, normo‐ or hypo‐cellular bone marrow (BM), who were treated cyclosporin A (CyA). Substantial haematological response was observed in 14 (82%): their improved and all transfusion‐dependent achieved transfusion independence. Complete trilineage recovery four (23%). The CyA therapy has not yet failed any the successfully during follow‐up times ranging from 5 to 30 months. well tolerated...
Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia thrombocytopenia.Patients were randomly assigned 1:1 to 300-mg or placebo 21 days/28-day cycle. The primary end point was transfusion independence (TI).Two hundred sixteen received (n = 107) 109). median age 74...
Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors TEs. However, the roles TEs piRNAs in MDS remain unclear. Methods In this study, we examined TE piRNA expression through parallel RNA sequencing CD34+ stem...
The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients higher-risk myelodysplastic syndromes (MDS). secondary objectives were assess symptom prevalence and examine the relationships between fatigue, quality life (QoL) overall burden these patients. analyses conducted 280 MDS Pre-treatment patient-reported evaluated Functional Assessment Chronic Illness Therapy (FACIT)-Fatigue scale QoL assessed European Organization for...
TP53 mutations are frequently detected in patients with higher-risk myelodysplastic syndromes (MDS); however, the clinical impact of these on disease course lower-risk MDS is unclear. In this study 154 patients, were identified 13% prevalence del(5q) (23.6%) compared to non-del(5q) (3.8%). Two-thirds at time diagnosis, and one-third during disease. Multivariate analysis demonstrated that a mutation was strongest independent prognostic factor for overall survival (OS) (HR: 4.39)...
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers disease. We aimed to characterize expression profiles sncRNAs MDS patients search for specific applicable biomarkers. performed RNA-seq in paired...
Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research. We generated set of transplantable murine PDX from MDS/AML patients who developed to compared the differences in hematopoiesis with bone marrow at genetic level. were...
Abstract Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive LR-MDS progression and uncover cellular pathways contributing malignant transformation. The mutational landscape was analyzed in 214 patients, at least one mutation detected 137 patients (64%). Mutated RUNX1 identified as the main predictor rapid by statistics machine...
Forty-eight patients with early myelodysplastic syndrome (MDS) without excess of blasts, average initial serum ferritin levels 2739.5 μg/L (range 825–11287 μg/L), were treated deferiprone (L1) in a daily dose 40–90 mg/kg. Median duration chelation treatment was 10.9 months 4–24 months). Chelation effective (maintained or decreased iron stores) 16 out 22 (73%) <2000 contrast to only 12 26 >2000 μg/L. Combination L1 recombinant human erythropoietin (rHuEPO) (30–40 kU/week) resulted five...
Downregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, importance CRBN patients myelodysplastic syndrome (MDS) its impact on therapy are not clear. In this study, we evaluate mononuclear cells isolated from bone marrow [23 lower risk MDS 5q deletion (5q-), 37 chromosome 5 without long arms (non-5q-), 24 healthy controls] peripheral blood (38 5q-, 52...
CCCTC-binding factor (CTCF) can both activate as well inhibit transcription by forming chromatin loops between regulatory regions and promoters. In this regard, Ctcf binding on non-methylated DNA its interaction with the Cohesin complex results in differential regulation of H19/Igf2 locus. Similarly, a role for CTCF has been established normal hematopoietic development; however involvement leukemia remains elusive. Here, we show that binds to imprinting control region AML blasts. We also...
Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent new class of biomarkers therapeutic targets, but information on their MDS limited. Aims: here, we aimed to characterize lncRNAs deregulated that may function disease In particular, focused the identification could serve as novel potential adverse outcomes MDS. Methods: performed microarray...
Red blood cell transfusions (RBCT) remain the cornerstone of supportive care in lower-risk myelodysplastic syndrome (LRMDS) [1]. Transfusion dependency LRMDS patients is associated with inferior outcomes, mainly attributed to severe bone marrow failure [2]. However, iron toxicity, due frequent RBCT or ineffective erythropoiesis, may be an additional negative prognostic factor [3,4,5,6]. Recently, much progress has been made unraveling metabolism. The peptide hormone hepcidin key regulator by...
BACKGROUND: Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction AZA responsiveness important therapy management. METHODS: Using microarrays reverse-transcription quantitative-PCR, we analyzed microRNA (miRNA) expression in bone marrow C D34+ cells 27 patients with higher-risk myelodysplastic syndromes or acute myeloid leukemia myelodysplasia-related changes before during treatment. RESULTS: At baseline, found that future overall response rate was...