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Sun, R.* ; He, L.* ; Lee, H.* ; Glinka, A.* ; Andrésen, C.* ; Hübschmann, D.* ; Jeremias, I. ; Müller-Decker, K.* ; Pabst, C.* ; Niehrs, C.*

RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia.

Cell Rep. 36:109559 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Acute myeloid leukemia (AML) is a rapidly progressing cancer, for which chemotherapy remains standard treatment and additional therapeutic targets are requisite. Here, we show that AML cells secrete the stem cell growth factor R-spondin 2 (RSPO2) to promote their self-renewal and prevent cell differentiation. Although RSPO2 is a well-known WNT agonist, we reveal that it maintains AML self-renewal WNT independently, by inhibiting BMP receptor signaling. Autocrine RSPO2 signaling is also required to prevent differentiation and to promote self-renewal in normal hematopoietic stem cells as well as primary AML cells. Comprehensive datamining reveals that RSPO2 expression is elevated in patients with AML of poor prognosis. Consistently, inhibiting RSPO2 prolongs survival in AML mouse xenograft models. Our study indicates that in AML, RSPO2 acts as an autocrine BMP antagonist to promote cancer cell renewal and may serve as a marker for poor prognosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acute Myeloid Leukemia ; Bmp ; Drug Resistance ; Hspc ; Leukemia Stem Cell ; Macrophages ; Monocytes ; R-spondin ; Self-renewal ; Wnt; Acute Myelogenous Leukemia; Hematopoietic Stem-cells; Wnt/beta-catenin; Wnt; Gene; Differentiation; Expression; Proteins; Cancer; Receptor
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 36, Heft: 7, Seiten: , Artikelnummer: 109559 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)
Förderungen Deutsche Forschungsgemeinschaft (DFG)
Max-Eder Grant of the German Cancer Aid
Deutsche Forschungsgemeinschaft