TY  - JOUR
A1  - Herrmann, Andreas B.
A1  - Müller, Martha‐Lena
A1  - Orth, Martin F.
A1  - Müller, Jörg P.
A1  - Zernecke, Alma
A1  - Hochhaus, Andreas
A1  - Ernst, Thomas
A1  - Butt, Elke
A1  - Frietsch, Jochen J.
T1  - Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance
JF  - Journal of Cellular and Molecular Medicine
N2  - 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.
KW  - BCR‐ABL
KW  - CML
KW  - CXCR4
KW  - LASP1
KW  - nilotinib
KW  - precursor cells
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214122
VL  - 24
IS  - 5
SP  - 2942
EP  - 2955
ER  -