Publications by authors named "Wolfgang Sperr"

Background: Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.

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The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation.

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  • - Mastocytosis is a disorder characterized by an abnormal increase of mast cells in one or more organs, with varying symptoms and outcomes; it's classified into cutaneous, systemic, and MC sarcoma types by the WHO.
  • - The disease often involves a specific mutation (D816V) in most systemic mastocytosis cases, affecting life expectancy significantly based on the type, with those having nonadvanced forms generally living near-normal lifespans, while advanced forms have limited life expectancies.
  • - Recently, a group of experts proposed updated diagnostic criteria and classifications for mastocytosis, aiming to unify different classifications from previous organizations to improve research and clinical comparisons.
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  • * Antifungal prophylaxis has reduced IFD occurrences but has also changed the types of fungal pathogens seen, necessitating broader screening methods for early diagnosis and treatment.
  • * A study analyzed blood samples from high-risk patients using advanced PCR techniques, revealing that many detectable fungi were typically non-pathogenic, highlighting the need for repeated testing and accurate identification to guide effective treatment.
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  • - Our study looked at fungal infections in patients with acute myeloid leukemia being treated with venetoclax and azacitidine, comparing those who received antifungal prophylaxis (AFP) to those who didn't.
  • - Out of 186 patients, only 1 out of 85 (1%) with AFP developed a fungal infection, while 5 out of 101 (5%) without AFP got infected, showing no significant difference between the two groups.
  • - Overall, the study found that fungal infections were mostly mild and appeared early in treatment, and they did not significantly impact patient survival or death rates.
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Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti-von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose.

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  • Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are serious blood cancers that involve the rapid increase of abnormal white blood cells, and recent research has highlighted BRD4 and MYC as potential targets for new drug therapies.
  • In experiments comparing various BRD4-targeting drugs, including the BET inhibitor JQ1 and BRD4 degraders dBET1 and dBET6, all three were effective at reducing the growth of AML and ALL cells, including resistant leukemic stem cells.
  • Notably, dBET6 outperformed the others by overcoming drug resistance, showing especially promising results when paired with other medications, and it also inhibited the expression of the resistance-related PD-L1 antigen in
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  • Mutations in the UBA1 gene, which are linked to VEXAS syndrome, have been found in patients with myelodysplastic syndromes (MDS), with a study identifying 7% of a cohort having specific UBA1 mutations.
  • An additional sequencing analysis of a larger group revealed 1% with other potentially harmful variants, and all 40 identified patients with likely/pathogenic mutations were male with various MDS subtypes.
  • Most patients with UBA1 mutations exhibited symptoms consistent with VEXAS syndrome, suggesting that routine screening for UBA1 mutations should be considered in MDS management.
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  • Hypersensitivity reactions (HR) are common in mastocytosis, a condition analyzed using data from the European Competence Network on Mastocytosis (ECNM), involving 2485 adults.
  • About 38.1% of patients reported HR, with Hymenoptera venoms being the primary trigger for cutaneous mastocytosis and indolent systemic mastocytosis, while drug reactions were more common in advanced systemic mastocytosis.
  • Key risk factors for HR include lower tryptase levels, minimal mast cell infiltration in bone marrow, and a diagnosis of indolent systemic mastocytosis, with new reactions occurring in 4.8% of patients over four years.
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Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter.

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A major problem in SARS-CoV-2-infected patients is the massive tissue inflammation in certain target organs, including the lungs. Mast cells (MC), basophils (BA), and eosinophils (EO) are key effector cells in inflammatory processes. These cells have recently been implicated in the pathogenesis of SARS-CoV-2 infections.

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Systemic mastocytosis (SM) is defined by the expansion and accumulation of neoplastic mast cells (MCs) in the bone marrow (BM) and extracutaneous organs. Most patients harbor a somatic KIT D816V mutation, which leads to growth factor-independent KIT activation and accumulation of MC. Tumor necrosis factor α (TNF) is a proapoptotic and inflammatory cytokine that has been implicated in the clonal selection of neoplastic cells.

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Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). In a vast majority of all patients, neoplastic cells display a mutation, mostly D816V and rarely other variants.

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The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear.

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Myelodysplastic syndromes (MDS) are myeloid neoplasms presenting with dysplasia in the bone marrow (BM) and peripheral cytopenia. In most patients anemia develops. We screened for genes that are expressed abnormally in erythroid progenitor cells (EP) and contribute to the pathogenesis of MDS.

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Physiological levels of basal serum tryptase vary among healthy individuals, depending on the numbers of mast cells, basal secretion rate, copy numbers of the TPSAB1 gene encoding alpha tryptase, and renal function. Recently, there has been a growing debate about the normal range of tryptase because individuals with the hereditary alpha tryptasemia (HαT) trait may or may not be symptomatic, and if symptomatic, uncertainty exists as to whether this trait directly causes clinical phenotypes or aggravates certain conditions. In fact, most HαT-positive cases are regarded as asymptomatic concerning mast cell activation.

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Introduction: The Vienna Cancer Stem Cell Club (VCSCC) was launched by a group of scientists in Vienna in 2002.

Areas Covered: Major aims of the VCSCC are to support research on cancer stem cells (CSC) in hematopoietic malignancies and to translate CSC-related markers and targets into clinical application. A primary focus of research in the VCSCC is the leukemic stem cell (LSC).

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Systemic mastocytosis (SM) is a hematopoietic neoplasm with a complex pathology and a variable clinical course. Clinical symptoms result from organ infiltration by mast cells (MC) and the effects of pro-inflammatory mediators released during MC activation. In SM, growth and survival of MC are triggered by various oncogenic mutant-forms of the tyrosine kinase KIT.

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In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists.

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Myeloproliferative neoplasms (MPN) are characterized by uncontrolled expansion of myeloid cells, disease-related mutations in certain driver-genes including JAK2, CALR, and MPL, and a substantial risk to progress to secondary acute myeloid leukemia (sAML). Although behaving as stem cell neoplasms, little is known about disease-initiating stem cells in MPN. We established the phenotype of putative CD34 /CD38 stem cells and CD34 /CD38 progenitor cells in MPN.

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  • * A study showed that CML patients had significantly more CD203c-positive leukocytes compared to healthy individuals, indicating a strong correlation between CD203c levels and disease risk.
  • * Successful treatment with medications like imatinib led to a notable decrease in CD203c basophils, suggesting that CD203c could be used as a biomarker to monitor basophilia in CML patients throughout their treatment journey.
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Patient-related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP).

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Background: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM).

Objectives: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM.

Methods: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed.

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Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may present as cutaneous mastocytosis or systemic mastocytosis (SM). On the basis of histopathological and molecular features, clinical variables, and organ involvement, SM is divided into indolent SM, smoldering SM, SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia.

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