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Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia.

Titel: Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1
Verfasser: Bäumer, Nicole GND
Bäumer, Sebastian Andreas GND
Berkenfeld, Frank
Stehling, Martin GND
Köhler, Gabriele
Berdel, Wolfgang E. GND
Müller-Tidow, Carsten GND
Tschanter, Petra Margret GND
Organisation: FB 05: Medizinische Fakultät
FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 19.12.2014
Publikation in MIAMI: 16.06.2015
Datum der letzten Änderung: 16.04.2019
Quelle: PLoS ONE 9 (2014) 12, e115578, 1-21
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-19239487121
DOI: 10.1371/journal.pone.0115578
ISSN: 1932-6203