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<datacite:identifier identifierType="URL">https://phaidra.vetmeduni.ac.at/o:3362</datacite:identifier>

  
<datacite:titles>
  
<datacite:title xml:lang="en">Phenotypic Characterization of Disease-Initiating Stem Cells in JAK2- or CALR-mutated Myeloproliferative Neoplasms</datacite:title>

  
</datacite:titles>

  
<datacite:creators>
  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Ivanov, Daniel</datacite:creatorName>

  
<datacite:givenName>Daniel</datacite:givenName>

  
<datacite:familyName>Ivanov</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0003-1304-4224</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Valent, Peter</datacite:creatorName>

  
<datacite:givenName>Peter</datacite:givenName>

  
<datacite:familyName>Valent</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0003-0456-5095</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Kralovics, Robert</datacite:creatorName>

  
<datacite:givenName>Robert</datacite:givenName>

  
<datacite:familyName>Kralovics</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-6997-8539</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Keil, Felix</datacite:creatorName>

  
<datacite:givenName>Felix</datacite:givenName>

  
<datacite:familyName>Keil</datacite:familyName>

  
<datacite:affiliation>Medical University of Vienna / Hanusch Hospital</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Gisslinger, Heinz</datacite:creatorName>

  
<datacite:givenName>Heinz</datacite:givenName>

  
<datacite:familyName>Gisslinger</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-0295-7629</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Pfeilstöcker, Michael</datacite:creatorName>

  
<datacite:givenName>Michael</datacite:givenName>

  
<datacite:familyName>Pfeilstöcker</datacite:familyName>

  
<datacite:affiliation>Medical University of Vienna / Hanusch Hospital</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Koller, Elisabeth</datacite:creatorName>

  
<datacite:givenName>Elisabeth</datacite:givenName>

  
<datacite:familyName>Koller</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-9912-0461</datacite:nameIdentifier>

  
<datacite:affiliation>Hanusch Hospital</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Speer, Wolfgang R.</datacite:creatorName>

  
<datacite:givenName>Wolfgang R.</datacite:givenName>

  
<datacite:familyName>Speer</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0003-3288-8027</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Bettelheim, Peter</datacite:creatorName>

  
<datacite:givenName>Peter</datacite:givenName>

  
<datacite:familyName>Bettelheim</datacite:familyName>

  
<datacite:affiliation>Krankenhaus der Elisabethinen</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Krauth, Maria-Theresa</datacite:creatorName>

  
<datacite:givenName>Maria-Theresa</datacite:givenName>

  
<datacite:familyName>Krauth</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0003-0662-3906</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Sliwa, Thamer</datacite:creatorName>

  
<datacite:givenName>Thamer</datacite:givenName>

  
<datacite:familyName>Sliwa</datacite:familyName>

  
<datacite:affiliation>Hanusch Hospital</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Fillitz, Michael</datacite:creatorName>

  
<datacite:givenName>Michael</datacite:givenName>

  
<datacite:familyName>Fillitz</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-5941-6751</datacite:nameIdentifier>

  
<datacite:affiliation>Hanusch Hospital</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Eisenwort, Gregor</datacite:creatorName>

  
<datacite:givenName>Gregor</datacite:givenName>

  
<datacite:familyName>Eisenwort</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0003-2735-4645</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Machherndl-Spandl, Sigrid</datacite:creatorName>

  
<datacite:givenName>Sigrid</datacite:givenName>

  
<datacite:familyName>Machherndl-Spandl</datacite:familyName>

  
<datacite:affiliation>Johannes Kepler University of Linz / Krankenhaus der Elisabethinen</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Hoermann, Gregor</datacite:creatorName>

  
<datacite:givenName>Gregor</datacite:givenName>

  
<datacite:familyName>Hoermann</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-7374-4380</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna / Munich Leukemia Laboratory</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Dahlhoff, Maik</datacite:creatorName>

  
<datacite:givenName>Maik</datacite:givenName>

  
<datacite:familyName>Dahlhoff</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0001-9189-7631</datacite:nameIdentifier>

  
<datacite:affiliation>University of Veterinary Medicine Vienna / Medical University of Vienna / University of Vienna / Center for Biomarker Research in Medicine</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Rülicke, Thomas</datacite:creatorName>

  
<datacite:givenName>Thomas</datacite:givenName>

  
<datacite:familyName>Rülicke</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-2121-9496</datacite:nameIdentifier>

  
<datacite:affiliation>University of Veterinary Medicine Vienna / Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Hadzijusufovic, Emir</datacite:creatorName>

  
<datacite:givenName>Emir</datacite:givenName>

  
<datacite:familyName>Hadzijusufovic</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0001-7409-4204</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Slavnitsch, Katharina</datacite:creatorName>

  
<datacite:givenName>Katharina</datacite:givenName>

  
<datacite:familyName>Slavnitsch</datacite:familyName>

  
<datacite:affiliation>University of Veterinary Medicine Vienna / Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Greiner, Georg</datacite:creatorName>

  
<datacite:givenName>Georg</datacite:givenName>

  
<datacite:familyName>Greiner</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-0917-4117</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna / Ihr labor</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Willmann, Michael</datacite:creatorName>

  
<datacite:givenName>Michael</datacite:givenName>

  
<datacite:familyName>Willmann</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0002-4260-1491</datacite:nameIdentifier>

  
<datacite:affiliation>University of Veterinary Medicine Vienna / Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Peter, Barbara</datacite:creatorName>

  
<datacite:givenName>Barbara</datacite:givenName>

  
<datacite:familyName>Peter</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0001-5701-5412</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Herrmann, Harald</datacite:creatorName>

  
<datacite:givenName>Harald</datacite:givenName>

  
<datacite:familyName>Herrmann</datacite:familyName>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Sadovnik, Irina</datacite:creatorName>

  
<datacite:givenName>Irina</datacite:givenName>

  
<datacite:familyName>Sadovnik</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0001-5418-5942</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
<datacite:creator>
  
<datacite:creatorName nameType="Personal">Milosevic Feenstra, Jelena D.</datacite:creatorName>

  
<datacite:givenName>Jelena D.</datacite:givenName>

  
<datacite:familyName>Milosevic Feenstra</datacite:familyName>

  
<datacite:nameIdentifier nameIdentifierScheme="ORCID" schemeURI="https://orcid.org/">0000-0001-7420-3298</datacite:nameIdentifier>

  
<datacite:affiliation>Medical University of Vienna</datacite:affiliation>

  
</datacite:creator>

  
</datacite:creators>

  
<dc:publisher>Wiley</dc:publisher>

  
<resourceType resourceTypeGeneral="literature" uri="http://purl.org/coar/resource_type/c_18cf">text</resourceType>

  
<dc:language>eng</dc:language>

  
<dc:description xml:lang="en">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. A total of 111 patients with MPN suffering from polycythemia vera, essential thrombocythemia, or primary myelofibrosis (PMF) were examined. In almost all patients tested, CD34+ /CD38- stem cells expressed CD33, CD44, CD47, CD52, CD97, CD99, CD105, CD117, CD123, CD133, CD184, CD243, and CD274 (PD-L1). In patients with PMF, MPN stem cells often expressed CD25 and sometimes also CD26 in an aberrant manner. MPN stem cells did not exhibit substantial amounts of CD90, CD273 (PD-L2), CD279 (PD-1), CD366 (TIM-3), CD371 (CLL-1), or IL-1RAP. The phenotype of CD34+ /CD38- stem cells did not change profoundly during progression to sAML. The disease-initiating capacity of putative MPN stem cells was confirmed in NSGS mice. Whereas CD34+ /CD38- MPN cells engrafted in NSGS mice, no substantial engraftment was produced by CD34+ /CD38+ or CD34- cells. The JAK2-targeting drug fedratinib and the BRD4 degrader dBET6 induced apoptosis and suppressed proliferation in MPN stem cells. Together, MPN stem cells display a unique phenotype, including cytokine receptors, immune checkpoint molecules, and other clinically relevant target antigens. Phenotypic characterization of neoplastic stem cells in MPN and sAML should facilitate their enrichment and the development of stem cell-eradicating (curative) therapies.</dc:description>

  
<datacite:subjects>
  
<datacite:subject xml:lang="en">Acute Myeloid-Leukemia; Polycythemia-Vera; Hematopoietic Stem; Progenitor Cells; Myelofibrosis; Transplantation; Expression; Target; Mice; Discoveries</datacite:subject>

  
</datacite:subjects>

  
<licenseCondition uri="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</licenseCondition>

  
<file mimeType="application/pdf" objectType="fulltext">https://phaidra.vetmeduni.ac.at/api/object/o:3362/download</file>

  
<datacite:alternateIdentifiers>
  
<datacite:alternateIdentifier alternateIdentifierType="DOI">10.1002/ajh.26889</datacite:alternateIdentifier>

  
</datacite:alternateIdentifiers>

  
<datacite:relatedIdentifiers>
  
<datacite:relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://phaidra.vetmeduni.ac.at/o:605</datacite:relatedIdentifier>

  
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<dc:format>application/pdf</dc:format>

  
<dc:source>American Journal of Hematology 98(5), 770-783 (2023)</dc:source>

  
<citationTitle>American Journal of Hematology</citationTitle>

  
<citationVolume>98</citationVolume>

  
<citationIssue>5</citationIssue>

  
<citationStartPage>770</citationStartPage>

  
<citationEndPage>783</citationEndPage>

  
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<datacite:size>4.07 MB</datacite:size>

  
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<datacite:dates>
  
<datacite:date dateType="Issued">2023</datacite:date>

  
</datacite:dates>

  
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