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dc.contributor.authorGelebart, Pascal Francois
dc.contributor.authorGjerstad, May Eriksen
dc.contributor.authorBenjaminsen, Susanne
dc.contributor.authorHan, Jianhua
dc.contributor.authorKarlsen, Ida
dc.contributor.authorMayoral Safont, Mireia
dc.contributor.authorLeitch, Calum
dc.contributor.authorFandalyuk, Zinayida
dc.contributor.authorPopa, Mihaela-Lucia
dc.contributor.authorHelgeland, Lars
dc.contributor.authorPapp, Bela
dc.contributor.authorBaran-Marszak, Fanny
dc.contributor.authorMc Cormack, Emmet
dc.date.accessioned2023-07-13T09:24:56Z
dc.date.available2023-07-13T09:24:56Z
dc.date.issued2023-06-20
dc.description.abstractMantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells. Interestingly, functional characterization of AXL3, using CRISPRi, revealed that only the knockdown of this isoform leads to apoptosis of MCL cells. Importantly, pharmacological inhibition of AXL activity resulted in a significant decrease in the activation of well-known pro-proliferative and survival pathways activated in MCL cells (i.e.b-catenin, AKT, and NF-kB). Therapeutically, pre-clinical studies using a xenograft mouse model of MCL indicated that bemcentinib is more effective than ibrutinib in reducing the tumour burden and to increase the overall survival. Our study highlights the importance of a previously unidentified AXL splice variant in cancer and the potential of bemcentinib as a targeted therapy for MCL.en_US
dc.identifier.citationGelebart, Gjerstad, Benjaminsen, Han, Karlsen, Mayoral Safont, Leitch, Fandalyuk, Popa, Helgeland, Papp, Baran-Marszak, Mc Cormack. Inhibition of a new AXL isoform (AXL3) induces apoptosis of mantle cell lymphoma cells. Blood. 2023en_US
dc.identifier.cristinIDFRIDAID 2161602
dc.identifier.doi10.1182/blood.2022015581
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.urihttps://hdl.handle.net/10037/29644
dc.language.isoengen_US
dc.publisherASH Publicationsen_US
dc.relation.journalBlood
dc.relation.projectIDKreftforeningen: 223171en_US
dc.relation.projectIDKreftforeningen: 182735en_US
dc.relation.projectIDNorges forskningsråd: 327278en_US
dc.relation.projectIDHelse Vest RHF: 911182en_US
dc.relation.projectIDNorges forskningsråd: 326300en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleInhibition of a new AXL isoform (AXL3) induces apoptosis of mantle cell lymphoma cellsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)