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Establishing a chemical genetic link between Bruton tyrosine kinase activity in malignant B cells and cell functions involved in the micro-environmental dialogue.
Göckeritz, Elisa; Vondey, Verena; Guastafierro, Anna; Pizevska, Maja; Hassenrück, Floyd; Neumann, Lars; Hallek, Michael; Krause, Günter.
Affiliation
  • Göckeritz E; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Vondey V; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Guastafierro A; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Pizevska M; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Hassenrück F; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Neumann L; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Hallek M; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
  • Krause G; Department I of Internal Medicine, University Hospital of Cologne, Centre of Integrated Oncology Cologne-Bonn, CECAD Centre of Excellence on "Cellular Stress Responses in Aging-associated Diseases", University of Cologne, Cologne, Germany.
Br J Haematol ; 178(6): 949-953, 2017 09.
Article in En | MEDLINE | ID: mdl-28573668
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein-Tyrosine Kinases / B-Lymphocytes / Leukemia, B-Cell / Lymphoma, B-Cell Limits: Humans Language: En Journal: Br J Haematol Year: 2017 Type: Article Affiliation country: Germany
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein-Tyrosine Kinases / B-Lymphocytes / Leukemia, B-Cell / Lymphoma, B-Cell Limits: Humans Language: En Journal: Br J Haematol Year: 2017 Type: Article Affiliation country: Germany