Schlafen 11 expression in human acute leukemia cells with gain-of-function mutations in the interferon-JAK signaling pathway.
Cell biology
Immunology
Molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Oct 2021
22 Oct 2021
Historique:
received:
25
05
2021
revised:
16
08
2021
accepted:
22
09
2021
entrez:
25
10
2021
pubmed:
26
10
2021
medline:
26
10
2021
Statut:
epublish
Résumé
Schlafen11 (SLFN11) is referred to as interferon (IFN)-inducible. Based on cancer genomic databases, we identified human acute myeloid and lymphoblastic leukemia cells with gain-of-function mutations in the Janus kinase (JAK) family as exhibiting high SLFN11 expression. In these cells, the clinical JAK inhibitors cerdulatinib, ruxolitinib, and tofacitinib reduced SLFN11 expression, but IFN did not further induce SLFN11 despite phosphorylated STAT1. We provide evidence that suppression of SLFN11 by JAK inhibitors is caused by inactivation of the non-canonical IFN pathway controlled by AKT and ERK. Accordingly, the AKT and ERK inhibitors MK-2206 and SCH77284 suppressed SLFN11 expression. Both also suppressed the E26 transformation-specific (ETS)-family genes ETS-1 and FLI-1 that act as transcription factors for SLFN11. Moreover, SLFN11 expression was inhibited by the ETS inhibitor TK216. Our study reveals that SLFN11 expression is regulated via the JAK, AKT and ERK, and ETS axis. Pharmacological suppression of SLFN11 warrants future studies.
Identifiants
pubmed: 34693224
doi: 10.1016/j.isci.2021.103173
pii: S2589-0042(21)01141-X
pmc: PMC8517841
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103173Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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