<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:date>2025</dc:date>
  <dc:source xml:lang="eng">Haematologica</dc:source>
  <dc:rights xml:lang="eng">©2024 Ferrata Storti Foundation</dc:rights>
  <dc:rights xml:lang="eng">open access</dc:rights>
  <dc:identifier>doi:10.3324/haematol.2024.285701</dc:identifier>
  <dc:publisher>Ferrata Storti Foundation</dc:publisher>
  <dc:type xml:lang="deu">Text</dc:type>
  <dc:type xml:lang="deu">Wissenschaftlicher Artikel</dc:type>
  <dc:rights>http://creativecommons.org/licenses/by/4.0/</dc:rights>
  <dc:description xml:lang="eng">Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C to be a key factor for B-cell ALL (B-ALL) development and maintenance. While cyclin C is not essential for normal hematopoiesis, Ccnc?/? BCR::ABL1+ B-ALL cells fail to elicit leukemia in mice. RNA sequencing experiments revealed a p53 pathway deregulation in Ccnc?/? BCR::ABL1+ cells resulting in the inability of the leukemic cells to adequately respond to stress. A genome-wide CRISPR/Cas9 loss-of-function screen supplemented with additional knock-outs unveiled a dependency of human B-lymphoid cell lines on CCNC. High cyclin C levels in B-cell precursor (BCP) ALL patients were associated with poor event-free survival and increased risk of early disease recurrence after remission. Our findings highlight cyclin C as a potential therapeutic target for B-ALL, particularly to enhance cancer cell sensitivity to stress and chemotherapy.</dc:description>
  <dc:subject xml:lang="eng">Tumor Suppressor Protein p53 Metabolism</dc:subject>
  <dc:subject xml:lang="eng">Tumor Suppressor Protein p53 Genetics</dc:subject>
  <dc:subject xml:lang="eng">Humans</dc:subject>
  <dc:subject xml:lang="eng">Animals</dc:subject>
  <dc:subject xml:lang="eng">Mice</dc:subject>
  <dc:subject xml:lang="eng">Cyclin C Metabolism</dc:subject>
  <dc:subject xml:lang="eng">Cyclin C Genetics</dc:subject>
  <dc:subject xml:lang="eng">Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Metabolism</dc:subject>
  <dc:subject xml:lang="eng">Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Pathology</dc:subject>
  <dc:subject xml:lang="eng">Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Genetics</dc:subject>
  <dc:subject xml:lang="eng">Stress, Physiological</dc:subject>
  <dc:subject xml:lang="eng">Disease Progression</dc:subject>
  <dc:subject xml:lang="eng">Cell Line, Tumor</dc:subject>
  <dc:creator>Jana Trifinopoulos</dc:creator>
  <dc:creator>Julia List</dc:creator>
  <dc:creator>Thorsten Klampfl</dc:creator>
  <dc:creator>Klara Klein</dc:creator>
  <dc:creator>Michaela Prchal-Murphy</dc:creator>
  <dc:creator>Agnieszka Witalisz-Siepracka</dc:creator>
  <dc:creator>Florian Bellutti</dc:creator>
  <dc:creator>Luca L. Fava</dc:creator>
  <dc:creator>Gerwin Heller</dc:creator>
  <dc:creator>Sarah Stummer</dc:creator>
  <dc:creator>Patricia Testori</dc:creator>
  <dc:creator>Monique L. Den Boer</dc:creator>
  <dc:creator>Judith M. Boer</dc:creator>
  <dc:creator>Sonja Marinovic</dc:creator>
  <dc:creator>Gregor Hoermann</dc:creator>
  <dc:creator>Wencke Walter</dc:creator>
  <dc:creator>Andreas Villunger</dc:creator>
  <dc:creator>Piotr Sicinski</dc:creator>
  <dc:creator>Veronika Sexl</dc:creator>
  <dc:creator>Dagmar Gotthardt</dc:creator>
  <dc:type xml:lang="ita">Testo</dc:type>
  <dc:type xml:lang="ita">Articolo di rivista</dc:type>
  <dc:type xml:lang="eng">Text</dc:type>
  <dc:type xml:lang="eng">journal article</dc:type>
  <dc:format>application/pdf</dc:format>
  <dc:language>eng</dc:language>
  <dc:title xml:lang="eng">Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses</dc:title>
  <dc:identifier>https://phaidra.vetmeduni.ac.at/o:4047</dc:identifier>
</oai_dc:dc>