Abstract：
:Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93 promotes gene transcription via the transcriptional regulator SCY1-like pseudokinase 1 independently of ligation of the extracellular domain. In a drug library screen, we identify the anti-emetic agent metoclopramide as an efficient blocker of CD93 signaling. Metoclopramide treatment reduces murine and human LSCs in vitro and prolongs survival of chronic myeloid leukemia (CML) mice through downregulation of pathways related to stemness and proliferation in LSCs. Overall, these results identify CD93 signaling as an LSC-specific regulator of self-renewal and proliferation and a targetable pathway to eliminate LSCs in CML.
journal_name
Cell Repjournal_title
Cell reportsauthors
Riether C,Radpour R,Kallen NM,Bürgin DT,Bachmann C,Schürch CM,Lüthi U,Arambasic M,Hoppe S,Albers CE,Baerlocher GM,Ochsenbein AFdoi
10.1016/j.celrep.2020.108663subject
Has Abstractpub_date
2021-01-26 00:00:00pages
108663issue
4issn
2211-1247pii
S2211-1247(20)31652-1journal_volume
34pub_type
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