Khalid Shoumariyeh
- Mast cells and histamine
- Eosinophilic Disorders and Syndromes
- Acute Myeloid Leukemia Research
- Asthma and respiratory diseases
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Urticaria and Related Conditions
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Food Allergy and Anaphylaxis Research
- Veterinary Oncology Research
- Cancer Genomics and Diagnostics
- Click Chemistry and Applications
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- Allergic Rhinitis and Sensitization
- Pancreatitis Pathology and Treatment
- Gastrointestinal Tumor Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
University of Freiburg
2017-2025
German Cancer Research Center
2018-2025
Heidelberg University
2018-2025
University Medical Center Freiburg
2014-2025
Deutschen Konsortium für Translationale Krebsforschung
2020-2023
University of Tsukuba Hospital
2019
University of Tsukuba
2019
Medical University of Vienna
2010
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Abstract Oncogenic Ras mutations occur in various leukemias. It was unclear if, besides the direct transforming effect via constant RAS/MEK/ERK signaling, an inflammation-related of KRAS contributes to disease. Here, we identify a functional link between oncogenic Kras G12D and NLRP3 inflammasome activation murine human cells. Mice expressing active hematopoietic system developed myeloproliferation cytopenia, which is reversed mice lacking system. Therapeutic IL-1-receptor blockade or...
To develop a risk score for patients with advanced systemic mastocytosis (AdvSM) that integrates clinical and mutation characteristics. The study included 383 AdvSM from the German Registry on Disorders of Eosinophils Mast Cells (training set; n = 231) several centers in United States Europe, all within European Competence Network Mastocytosis (validation 152). A Cox multivariable model was used to select variables were predictive overall survival (OS). In analysis, following factors...
Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis. We found that T cells of patients relapsing with AML allo-HCT exhibited reduced glycolysis and interferon-γ production. Functional studies in multiple mouse models showed leukemia-derived lactic acid (LA) interfered proliferation. Mechanistically, LA intracellular pH cells, led to lower transcription glycolysis-related enzymes, decreased activity essential metabolic...
Abstract Successful treatment of acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) T cells is hampered by toxicity on normal hematopoietic progenitor and low CAR cell persistence. Here, we develop third-generation anti-CD123 a humanized CSL362-based ScFv CD28-OX40-CD3ζ intracellular signaling domain. This demonstrates anti-AML activity without affecting the healthy system, or causing epithelial tissue damage in xenograft model. CD123 expression increases upon 5′-Azacitidine...
Abstract Background In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, also shown that the clinical course in ISM is stable and comparable to cutaneous (CM). The aim this project was compare prognosis patients CM. Methods We employed a dataset 1993 from registry European Competence Network on Mastocytosis (ECNM) outcomes Results found overall survival (OS) worse compared...
Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field second, provide access broad patient population. Here, we report four-year experience of the Tumor Board (MTB) Comprehensive Cancer Center Freiburg (Germany) including workflows process optimizations. This retrospective single-center study includes data on 488 patients enrolled MTB from February 2015 through December 2018. Recommendations include...
Abstract Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network Mastocytosis registry. Thirty-one (34%) had diagnosis an associated hematologic neoplasm (MCL-AHN). Chronic (lack C-findings) comprised 14% patients, and only 4.5% “leukemic MCL” (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited...
Abstract Individuals with hematologic malignancies are at increased risk for severe coronavirus disease 2019 (COVID-19), yet profound analyses of COVID-19 vaccine-induced immunity scarce. Here we present an observational study expanded methodological analysis a longitudinal, primarily BNT162b2 mRNA-vaccinated cohort 60 infection-naive individuals B cell lymphomas and multiple myeloma. We show that many these individuals, despite markedly lower anti-spike IgG titers, rapidly develop potent...
Abstract We identified 71 patients with AdvSM (aggressive SM [ASM], an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received allogeneic hematopoietic transplantation (alloHCT) performed Germany from 1999–2021. Median overall survival (OS) of ASM/SM-AHN ( n = 30, 45%), SM-AML 28, 39%) and MCL ± AHN 13, 19%) was 9.0, 3.3 0.9 years P 0.007). Improved median OS response (17/41, 41%; HR 0.4...
Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies a larger cohort mastocytosis patients. We assessed prevalence, factors HR adults with ECNM registry.
In systemic mastocytosis (SM), the clinical features and survival vary greatly.Patient-related factors determining outcome in SM are largely unknown. Ivyspring International
Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics leukocytes from corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved histological GVHD severity mice was...
KIT D816 mutations (KIT D816mut) are strongly associated with systemic mastocytosis (SM) but also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor combination core binding (CBF) fusion genes. Here, we evaluated the clinical and molecular features of D816mut/CBF-negative (CBFneg) AML, a previously uncharacterized combination. All D816mut/CBFneg cases (n = 40) had histologically proven SM AML (SM-AML). Molecular analyses revealed at least one...
Abstract Background Patients with cancer are considered a high‐risk group for viral pneumonia, an increased probability of fatal outcome. Here, we investigated the clinical characteristics and outcome patients solid hematological cancers concomitant Covid‐19 at Comprehensive Cancer Center in hotspot area Germany. Methods We performed retrospective single center cohort study 39 who were hospitalized University Hospital Freiburg Covid‐19. Using univariate multivariate Cox regression models...
ObjectiveMeasuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint an intra-patient progression-free survival (PFS) ratio, defined as PFS interval associated with therapy (PFS2) divided by last prior systemic (PFS1), above 1.3 or, some studies, 1.33 or 1.5.MethodsTo investigate if concept ratios agreement actual response evaluations physicians, we conducted survey among members MASTER (Molecularly Aided Stratification...
Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) the classification World Health Organization and International Consensus Classification. So far, it remains unknown whether expression these antigens on MC prognostic significance SM. We performed retrospective multi-center study patients with SM using data set registry European Competence Network Mastocytosis, including 5034 various disorders. The percentage...
ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that characterized by expression of the Kinase (ALK), which induced t(2;5) chromosomal rearrangement leading to NPM-ALK fusion-oncogene. Most previous preclinical models ALCL were based on overexpression cDNA from heterologous promoters. Due enforced expression, this approach prone artifacts arising synthetic overexpression, promoter competition and insertional variation. To improve existing more closely recapitulate...