Publications by authors named "Pleyer L"

Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs): enhancers and silencers. Although enhancers have been thoroughly characterized, the properties and mechanisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs as they mostly lack detectable DNA accessibility.

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Background And Aims: To evaluate, if high frame rate (HiFR) contrast-enhanced ultrasound (CEUS) and external perfusion analysis (VueBox®)can give answers on liver tumour diagnostics.

Methods: A multifrequency probe (C1-6 /Resona R9) and 1-2.4 ml ultrasound contrast medium were used for CEUS up to 5-6 min.

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Article Synopsis
  • Acute myeloid leukemia (AML) is a serious blood cancer that is hard to treat, and scientists are studying a part of the immune system called the NLRP3 inflammasome to understand its role in AML.
  • Researchers looked at gene expressions in AML patients and created special cells to study how NLRP3 affects AML cell survival.
  • They found that higher levels of NLRP3 are linked to worse outcomes for patients, and blocking NLRP3 helps make AML cells die, which could lead to new treatments for the disease.
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  • - Chronic myelomonocytic leukemia (CMML) is a complex disease that can display both myeloproliferative and myelodysplastic characteristics, making treatment decisions particularly challenging for older patients with other health issues.
  • - Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only potential cure for CMML, but due to the procedure's toxicity and lack of definitive studies, the choice between allo-HCT and less intensive treatments requires careful consideration.
  • - The European Society for Blood and Marrow Transplantation has released new best practice recommendations for allo-HCT in CMML, emphasizing that if patients are candidates for transplantation, it should ideally be done upfront, without prior treatments,
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Introduction: Targeting the B-cell receptor pathway via ibrutinib, a specific inhibitor of Bruton's tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred first line option independent of risk factors. However, acquired resistance to ibrutinib poses a major clinical problem and requires the development of novel treatment combinations to increase efficacy and counteract resistance development and clinical relapse rates.

Case Presentation: In this study, we performed exome and transcriptome analyses of an ibrutinib resistant CLL patient in order to investigate genes and expression patterns associated with ibrutinib resistance.

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The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment.

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: Next generation sequencing (NGS) has become indispensable for diagnosis, risk stratification, prognostication, and monitoring of response in patients with myeloid neoplasias. Guidelines require bone marrow evaluations for the above, which are often not performed outside of clinical trials, indicating a need for surrogate samples. : Myeloid NGS analyses (40 genes and 29 fusion drivers) of 240 consecutive, non-selected, prospectively collected, paired bone marrow/peripheral blood samples were compared.

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Recruitment of RNA polymerase II (Pol II) to promoters is essential for transcription. Despite conflicting evidence, the Pol II preinitiation complex (PIC) is often thought to have a uniform composition and to assemble at all promoters via an identical mechanism. Here, using Drosophila melanogaster S2 cells as a model, we demonstrate that different promoter classes function via distinct PICs.

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In this prospective study (NCT01595295), 272 patients treated with azacitidine completed 1456 EuroQol 5-Dimension (EQ-5D) questionnaires. Linear mixed-effect modelling was used to incorporate longitudinal data. When compared with a matched reference population, myeloid patients reported more pronounced restrictions in usual activities (+28%, < 0.

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Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by altered myeloid progenitor cell proliferation and differentiation. As in many other cancers, epigenetic transcriptional repressors such as histone deacetylases (HDACs) are dysregulated in AML. Here, we investigated (1) HDAC gene expression in AML patients and in different AML cell lines and (2) the effect of treating AML cells with the specific class IIA HDAC inhibitor TMP269, by applying proteomic and comparative bioinformatic analyses.

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Background: Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) comprise several rare hematologic malignancies with shared concomitant dysplastic and proliferative clinicopathologic features of bone marrow failure and propensity of acute leukemic transformation, and have significant impact on patient quality of life. The only approved disease-modifying therapies for any of the MDS/MPN are DNA methyltransferase inhibitors (DNMTi) for patients with dysplastic CMML, and still, outcomes are generally poor, making this an important area of unmet clinical need. Due to both the rarity and the heterogeneous nature of MDS/MPN, they have been challenging to study in dedicated prospective studies.

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Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents.

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Acute myeloid leukemia (AML) cells can secrete trophic factors, including extracellular vesicles (EVs), instructing the stromal leukemic niche. Here, we introduce a scalable workflow for purification of immunomodulatory AML-EVs to compare their phenotype and function to the parental AML cells and their secreted soluble factors. AML cell lines HL-60, KG-1, OCI-AML3, and MOLM-14 released EVs with a peak diameter of approximately 80 nm in serum-free particle-reduced medium.

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Article Synopsis
  • The study investigates the effectiveness of hypomethylating agents in treating patients with chronic myelomonocytic leukaemia (CMML) by comparing their outcomes to those receiving other treatments, like hydroxyurea and intensive chemotherapy.
  • Data was collected retrospectively from 949 patients across 38 centers in the USA and Europe between late 2017 and early 2019, focusing on overall survival and treatment progression.
  • Findings showed that patients first treated with hypomethylating agents had a median overall survival of 20.7 months, which was better compared to 15.6 months for those treated with hydroxyurea, indicating potential benefits of hypomethylating agents in this patient group.
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Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation.

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Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed.

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No data are available regarding obesity and outcome in Chronic Lymphocytic Leukemia (CLL). We analyzed 263 patients from the AGMT CLL-8a Mabtenance trial for the impact of obesity. The trial included patients after rituximab-containing induction treatment in first or second line that had achieved at least a PR.

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Acute myeloid leukemia (AML) is a clonal disease caused by genetic abberations occurring predominantly in the elderly. Next generation sequencing (NGS) analysis has led to a deeper genetic understanding of the pathogenesis and the role of recently discovered genetic precursor lesions (clonal hematopoiesis of indeterminate/oncogenic potential (CHIP/CHOP)) in the evolution of AML. These advances are reflected by the inclusion of certain mutations in the updated World Health Organization (WHO) 2016 classification and current treatment guidelines by the European Leukemia Net (ELN) and National Comprehensive Cancer Network (NCCN) and results of mutational testing are already influencing the choice and timing of (targeted) treatment.

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  • Acute myeloid leukemia (AML) primarily affects older adults, and treatment options are limited after hypomethylating agents (HMA) fail, leading to poor survival rates.
  • A case series in Salzburg, Austria, treated seven patients with secondary AML (sAML) who were not suitable for intensive chemotherapy and had previously not responded to HMA with the BCL-2 inhibitor venetoclax.
  • The results showed that two patients achieved complete remission, with significant overall survival differences between responders (average 364 days) and non-responders (average 24 days), indicating that venetoclax is a promising option for treatment after HMA failure.
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  • The AGMT exercise study investigated the effects of physical training on 50 postmenopausal breast cancer patients undergoing aromatase inhibitor treatment, focusing on the feasibility and efficacy of exercise.
  • Patients were divided into two groups: one received unsupervised training while the other engaged in supervised exercise for the first 24 weeks followed by unsupervised training.
  • Results showed that the supervised group significantly increased their maximum power output and weekly physical activity levels compared to the unsupervised group, suggesting that supervised exercise programs are more effective in enhancing fitness in these patients.
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Chronic lymphocytic leukemia (CLL) treatment has come a long way in the last two decades, producing increases in tumor control to the point of generating sizeable numbers of patients with undetectable minimal residual disease and creating overall survival benefits in randomized comparisons. Most of this has been achieved by limited-term treatment approaches including chemotherapeutic and immune-therapeutic drugs. More recently, novel therapies targeting signaling pathways essential for the survival of the neoplastic clones have opened avenues that provide disease control in long-term treatment designs, mostly without producing deep remissions.

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Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients after HMA failure.

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