Goeckeritz, Elisa, Vondey, Verena, Guastafierro, Anna, Pizevska, Maja, Hassenrueck, Floyd, Neumann, Lars, Hallek, Michael and Krause, Guenter (2017). Establishing a chemical genetic link between Bruton tyrosine kinase activity in malignant B cells and cell functions involved in the micro-environmental dialogue. Br. J. Haematol., 178 (6). S. 949 - 954. HOBOKEN: WILEY. ISSN 1365-2141

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Abstract

To elucidate their mechanism of action, inhibitors of Bruton tyrosine kinase (BTK) and resistant BTK mutants were employed to dissect target-dependent cellular functions. BTK-C481S and -T474I, expressed in Ramos and NALM-6 cells, maintained BTK auto-phosphorylation under treatment with ibrutinib or dasatinib, respectively, which showed only modest cytotoxicity. Retained activity of BTK-T474 partially rescued cell migration from inhibition by dasatinib. Importantly, resistant BTK mutants reconstituted B cell receptor-triggered chemokine secretion in the presence of corresponding inhibitors, demonstrating that BTK activity is connected with cell-intrinsic functions of malignant B cells with importance for their dialogue with the micro-environment.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Goeckeritz, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vondey, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guastafierro, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pizevska, MajaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassenrueck, FloydUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-219345
DOI: 10.1111/bjh.14781
Journal or Publication Title: Br. J. Haematol.
Volume: 178
Number: 6
Page Range: S. 949 - 954
Date: 2017
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1365-2141
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-MICROENVIRONMENT; IN-VIVO; INHIBITORS; IBRUTINIB; DASATINIB; SURVIVALMultiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21934

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