5 results on '"Katharina Slavnitsch"'
Search Results
2. Phenotypic characterization of disease‐initiating stem cells in JAK2 ‐ or CALR ‐mutated myeloproliferative neoplasms
- Author
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Daniel Ivanov, Jelena D. Milosevic Feenstra, Irina Sadovnik, Harald Herrmann, Barbara Peter, Michael Willmann, Georg Greiner, Katharina Slavnitsch, Emir Hadzijusufovic, Thomas Rülicke, Maik Dahlhoff, Gregor Hoermann, Sigrid Machherndl‐Spandl, Gregor Eisenwort, Michael Fillitz, Thamer Sliwa, Maria‐Theresa Krauth, Peter Bettelheim, Wolfgang R. Sperr, Elisabeth Koller, Michael Pfeilstöcker, Heinz Gisslinger, Felix Keil, Robert Kralovics, and Peter Valent
- Subjects
Hematology - Published
- 2023
3. Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia
- Author
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Daniela Berger, Alexandra Keller, Georg Greiner, Daniel Ivanov, Thomas Rülicke, Peter Bettelheim, Michael W. Deininger, Irina Sadovnik, Heinz Sill, Karin Bauer, Michael Willmann, Karoline V. Gleixner, Wolfgang R. Sperr, Gregor Eisenwort, Barbara Peter, Peter Valent, Gabriele Stefanzl, Katharina Slavnitsch, and Klaus Geissler
- Subjects
Male ,0301 basic medicine ,Cancer Research ,CD52 ,CD33 ,Chronic myelomonocytic leukemia ,Antigens, CD34 ,Apoptosis ,Mice, SCID ,Biology ,CD38 ,Article ,Venetoclax ,Mice ,03 medical and health sciences ,0302 clinical medicine ,AML ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Secondary Acute Myeloid Leukemia ,Aged ,Cell Proliferation ,Aged, 80 and over ,Leukemia, Myelomonocytic, Chronic ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Leukemic Stem Cells ,Leukemia, Myeloid, Acute ,Leukemia ,Phenotype ,030104 developmental biology ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,NSGS Mice ,Neoplastic Stem Cells ,Cancer research ,Female ,sense organs ,Interleukin-3 receptor ,Stem cell - Abstract
Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34+/CD38– fraction of the malignant clone. Whereas CD34+/CD38– cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34+/CD38+ progenitors or the bulk of CD34– monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34+/CD38– cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies.
- Published
- 2021
4. Phenotyping of Disease-Initiating CD34+/CD38─ Stem Cells in BCR-ABL1─ MPN Reveals Expression of Multiple Cytokine Receptors and Resistance-Related Antigens
- Author
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Georg Greiner, Daniel Ivanov, Katharina Slavnitsch, Robert Spörk, Alexandra Keller, Michael Fillitz, Gregor Eisenwort, Klaus Geissler, Robert Kralovics, Michael Willmann, Jelena D. Milosevic Feenstra, Peter Valent, Michael Pfeilstöcker, Thamer Sliwa, Elisabeth Koller, Gabriele Stefanzl, Heinz Sill, Peter Bettelheim, Felix Keil, Sybille Hofer, Thomas Rülicke, Gregor Hoermann, Wolfgang R. Sperr, and Barbara Peter
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Immunology ,CD44 ,CD34 ,food and beverages ,Stem cell factor ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology ,medicine.anatomical_structure ,medicine ,biology.protein ,CD90 ,IL-2 receptor ,Bone marrow ,Stem cell ,Progenitor cell - Abstract
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) are characterized by over-production of myeloid cells, disease-related mutations in certain driver-genes (JAK2, CALR, MPL) and an increased risk to transform to secondary acute myeloid leukemia (sAML). Although considered stem cell-derived neoplasms, little is known about the phenotype and functional properties of disease-initiating neoplastic stem cells (NSC) in MPN and sAML. Recent data suggest that MPN NSC reside in a CD34+ fraction of the malignant clone. Therefore, these cells are considered most critical target populations to be examined for expression of molecular and immunological targets with the aim to develop improved or even curative NSC-eliminating therapies, such as antibody-based or CAR-T cell approaches. Using a panel of monoclonal antibodies (n=40) and multicolor flow cytometry, we established the immunological phenotype and target expression profiles of putative CD34+/CD38─ NSC and CD34+/CD38+ progenitor cells in patients with polycythemia vera (PV, n=18), essential thrombocythemia (ET, n=29), primary myelofibrosis (PMF, n=38) and post-MPN sAML (n=11). In almost all patients, the putative MPN stem cells expressed the stem cell invasion receptors Hermes (CD44) and ADGRE5 (CD97), C1qR1 (CD93), the migration/adhesion receptor MIC2 (CD99), and the stem cell antigen AC133 (CD133). Contrasting normal stem cells, MPN NCS and sAML stem cells failed to express Thy-1 (CD90). Among the cytokine receptors tested, MPN NSC invariably displayed the TGFßR-related antigen endoglin (CD105), TPOR (CD110), SCFR KIT (CD117), IL-3RA (CD123), CXCR4 (CD184) and IGF-1R (CD221). NSC expressed particularly high levels of KIT and low levels of TPOR and IGF-1R. The IL-2RA (CD25) was identified on NSC in most patients with PMF and sAML, and in a few with ET, but not in patients with PV. Similarly, the GM-CSFR (CD116) was found to be expressed on NSC in most patients with PMF, a few with ET and no with PV. MPN NSC did not exhibit substantial amounts of M-CSFR (CD115), IL-3RB (CD131), FLT3 (CD135), NGFR (CD271) VEGFR-2 KDR (CD309), EPOR, MET or OSMRB. The CD34+/CD38+ MPN progenitor cells displayed a similar profile of cytokine receptors. In addition, MPN and sAML progenitor cells expressed IL-1RAP and CLL-1 in most donors examined. We next examined the expression of various immunological targets and resistance-mediating immune checkpoint antigens on NSC and MPN progenitor cells. In all MPN patients and all sAML patients tested, NSC were found to express substantial amounts of Siglec-3 (CD33) and low levels of Campath-1 (CD52) and MDR-1 (CD243). In addition, MPN NSC and sAML stem cells invariably displayed the "don't eat" me checkpoint IAP (CD47) and the classical checkpoint PD-L1 (CD274). Exposure to interferon-gamma (200 U/ml, 24 hours) resulted in an upregulation of PD-L1 on NSC. In a subset of patients, MPN NSC expressed low levels of HB15 (CD83). In contrast, MPN NSC and sAML stem cells failed to express B7-1 (CD80), B7-2 (CD86), PD-L2 (CD273) and PD1 (CD279). MPN progenitor cells and sAML progenitors expressed an identical profile of cell surface targets and checkpoint antigens. Finally, we confirmed the disease-initiating capacity of MPN stem- and progenitor cells (CD34+ cells) using primary PMF cells in xenotransplantation experiments employing NSGS mice expressing human interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF). After 28 weeks post injection, engraftment of human CD45+ cells in the bone marrow of NSGS mice was found in 15/15 mice injected with bulk mononuclear cells (MNC) containing CD34+ cells and in 0/15 NSGS mice injected with MNC depleted of CD34+ cells. Together, MPN NSC reside in a CD34+ fraction of the malignant clone and display a unique phenotype, including cytokine receptors, immune checkpoint molecules and other target antigens. The phenotypic characterization of neoplastic stem cells should facilitate their enrichment and the development of NSC-eradicating treatment concepts in MPN. Disclosures Valent: Allcyte GmbH: Research Funding; Pfizer: Honoraria; Cellgene: Honoraria, Research Funding.
- Published
- 2020
5. IC‐P‐073: A New Biogenic hAPP x hTau Mouse Model Shows Progressive Brain Pathology and Behavioral Disturbance
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Manfred Windisch, Katharina Slavnitsch, Stephan Duller, Heinz Hutter, and Birgit Hutter-Paier
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Pathology ,medicine.medical_specialty ,Disturbance (geology) ,Developmental Neuroscience ,Epidemiology ,Health Policy ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Biology ,Neuroscience - Published
- 2010
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