A5030747264- Chronic Lymphocytic Leukemia Research
- Cancer Mechanisms and Therapy
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Thyroid Cancer Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- T-cell and Retrovirus Studies
- Cancer-related Molecular Pathways
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Kruppel-like factors research
- Phagocytosis and Immune Regulation
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Neuroendocrine Tumor Research Advances
- Immune cells in cancer
- Multiple Myeloma Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- Eosinophilic Disorders and Syndromes
- Cytokine Signaling Pathways and Interactions
University of Freiburg
2014-2024
Martin Luther University Halle-Wittenberg
2021-2024
University Medical Center
2024
University Medical Center Freiburg
2011-2023
University Hospital in Halle
2021-2023
University Hospital of Zurich
2019
NIHR CRUK Experimental Cancer Medicine Centre
2019
Cancer Research UK
2019
Praxis für Hämatologie und Onkologie
2019
University of Zurich
2019
Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 cells from 12 samples, that a subset Interleukin-10-releasing HMOX1
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors highly proliferative, frequently increased tumor mutational burden (TMB) compared carcinomas, elevated programmed death ligand 1 (PD-L1) levels. properties implicate responsiveness to antiangiogenic antiproliferative multikinase inhibitors such as lenvatinib, immune checkpoint pembrolizumab.
Abstract B-cell receptor signaling contributes to apoptosis resistance in chronic lymphocytic leukemia (CLL), limiting the efficacy of current therapeutic approaches. In this study, we investigated expression spleen tyrosine kinase (SYK), a key component pathway, CLL and its role apoptosis. Gene profiling identified enhanced SYK downstream pathways compared with healthy B cells. Immunoblotting showed increased phosphorylation SYK, PLCγ2, signal transducers activators transcription 3,...
FLT3-ITD–mediated leukemogenesis is associated with increased expression of oncogenic PIM serine/threonine kinases. To dissect their role in transformation, we performed bone marrow reconstitution assays. Unexpectedly, FLT3-ITD cells deficient for PIM1 failed to reconstitute lethally irradiated recipients, whereas lack PIM2 induction did not interfere FLT3-ITD–induced disease. PIM1-deficient showed defects homing and migration displayed decreased surface CXCR4 impaired CXCL12–CXCR4...
Dramatic advances in our understanding of the molecular pathophysiology cancer, along with a rapidly expanding portfolio targeted drugs, have led to paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report 2-year experience Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one first interdisciplinary tumor conferences established Europe. The role MTB is recommend personalized therapy for patients beyond standard-of-care
Despite recent advances, the myeloproliferative neoplasms (MPNs) are attended by considerable morbidity and mortality. Janus kinase (Jak) inhibitors such as ruxolitinib manage symptoms but do not substantially change natural history of disease. In this report, we show effects IMG-7289, an irreversible inhibitor epigenetically active lysine-specific demethylase 1 (LSD1) in mouse models MPN. Once-daily treatment with IMG-7289 normalized or improved blood cell counts, reduced spleen volumes,...
The molecular etiology of myeloproliferative neoplasms (MPNs) remains incompletely understood, despite recent advances incurred through the discovery several different mutations in MPN patients. We have recently described overexpression transcription factor NF-E2 patients and shown that elevated levels vivo cause an phenotype predispose to leukemic transformation transgenic mice. report presence acquired insertion deletion gene These result truncated proteins enhance wild-type (WT) function...
Overexpression of the CXCR4 receptor is a hallmark chronic lymphocytic leukemia (CLL) and important for CLL cell survival, migration, interaction with their protective microenvironment. In acute myelogenous (AML), PIM1 was shown to regulate surface expression receptor. Here, we show that PIM (proviral integration site Moloney murine virus) kinases 1-3 are overexpressed hyperphosphorylated on Ser339 in compared normal lymphocytes. Furthermore, phosphorylation correlates protein transcript...
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 Peripheral T-cell lymphomas (PTCL) constitute a major treatment problem with high mortality rates due to the minimal effectiveness of conventional chemotherapy. Recent findings identified ITK-SYK as first recurrent translocation in 17% unspecified PTCLs and showed overexpression SYK more than 90% PTCLs. Here, we show that expression bone marrow BALB/c mice causes lymphoproliferative disease all transplanted within 8 weeks after transplantation. The was characterized by infiltration...
Background Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 approved advanced radioiodine refractory carcinoma, but response to single agent poor in ATC. Recent reports of combining LEN with PD-1 pembrolizumab (PEM) promising. Materials Methods Primary ATC (n=93) PDTC (n=47) tissue samples...
JAK2V617F+ myeloproliferative neoplasms (MPNs) frequently progress into leukemias, but the factors driving this process are not understood. Here, we find excess Hedgehog (HH) ligand secretion and loss of PTCH2 in disease, which drives canonical noncanonical HH-signaling. Interestingly, Ptch2−/− mice mimic dual pathway activation develop a MPN-phenotype with leukocytosis (neutrophils monocytes), strong progenitor LKS mobilization, splenomegaly, anemia, lymphoid lineages. HSCs exhibit...
Summary Direct contact with stromal cells protects chronic lymphocytic leukaemia (CLL) B from chemotherapy‐induced apoptosis in vitro . Blockade of CXCR4 signalling antagonizes stroma‐mediated interactions and restores CLL chemosensitivity. In vivo , administration antagonists effectively mobilizes haematopoietic progenitor cells. Therefore, combinations blockade cytoreductive treatment selective activity on may avoid potential haematotoxicity. Hence, we tested the context passive active...