Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance

Herrmann AB, Mueller ML, Orth MF, Mueller JP, Zernecke A, Hochhaus A, Ernst T, Butt E, Frietsch JJ (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Journal of Cellular and Molecular Medicine Wiley-Blackwell / Wiley Open Access

Book Volume: 24

Pages Range: 2942-2955

Journal Issue: 5

DOI: 10.1111/jcmm.14910

Abstract

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 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.

Involved external institutions

Universitätsklinikum Jena DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Herrmann, A.B., Mueller, M.-L., Orth, M.F., Mueller, J.P., Zernecke, A., Hochhaus, A.,... Frietsch, J.J. (2020). Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance. Journal of Cellular and Molecular Medicine, 24(5), 2942-2955. https://doi.org/10.1111/jcmm.14910

MLA:

Herrmann, Andreas B., et al. "Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance." Journal of Cellular and Molecular Medicine 24.5 (2020): 2942-2955.

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