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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)
Publ. Version/Full Text Research data 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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Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 36, Issue: 7, Pages: , Article Number: 109559 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Stem Cell and Neuroscience
PSP Element(s) G-506600-001
Grants Deutsche Forschungsgemeinschaft (DFG)
Max-Eder Grant of the German Cancer Aid
Deutsche Forschungsgemeinschaft
DOI 10.1016/j.celrep.2021.109559
WOS ID WOS:000686356500022
Scopus ID 85112845054
PubMed ID 34407399
Erfassungsdatum 2021-09-21
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