TY  - JOUR
AB  - External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.
AU  - Bäumer, Nicole
AU  - Baumer, Nicole
AU  - Krause, Annika
AU  - Köhler, Gabriele
AU  - Lettermann, Stephanie
AU  - Evers, Georg Heribert
AU  - Hascher, Antje
AU  - Bäumer, Sebastian Andreas
AU  - Berdel, Wolfgang E.
AU  - Berdel, Wolfgang
AU  - Berdel, W. E.
AU  - Müller-Tidow, Carsten
AU  - Tickenbrock, Lara
DA  - 2014-04-16
DO  - doi:10.1371/journal.pone.0094993
LA  - eng
N1  - PLOS One 9 (2014) 4, 1-13, e94993
N1  - Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2014-04-16
SN  - 1932-6203
TI  - Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-41359407251
Y2  - 2024-11-22T05:28:11
ER  -