Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-214122
- Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR‐ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR‐ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1‐mediated pathways and related factorsChronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR‐ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR‐ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1‐mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell‐mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.…
Autor(en): | Andreas B. HerrmannORCiD, Martha‐Lena Müller, Martin F. Orth, Jörg P. Müller, Alma Zernecke, Andreas Hochhaus, Thomas Ernst, Elke Butt, Jochen J. Frietsch |
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URN: | urn:nbn:de:bvb:20-opus-214122 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Medizinische Fakultät / Institut für Experimentelle Biomedizin | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Journal of Cellular and Molecular Medicine |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 24 |
Heft / Ausgabe: | 5 |
Erste Seite: | 2942 |
Letzte Seite: | 2955 |
Originalveröffentlichung / Quelle: | Journal of Cellular and Molecular Medicine 2020, 24(5):2942-2955. DOI: 10.1111/jcmm.14910 |
DOI: | https://doi.org/10.1111/jcmm.14910 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | BCR‐ABL; CML; CXCR4; LASP1; nilotinib; precursor cells |
Datum der Freischaltung: | 15.04.2021 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |