INTERFERON ALPHA AND KINASE INHIBITOR NILOTINIB INCREASE CELL ADHESION AND TUNNELING NANOTUBES IN CML

Summary statementThis study describes the effects of tyrosine kinase inhibitors on tunneling nanotube formation via increased adhesion through {beta}-integrin in chronic myeloid leukemia cells.\n\nAbstractThe actin-containing cell-to-cell communicator tunneling nanotube (TNT) is involved in regulation of cell death threshold of leukemic cells, while the mechanism of TNT regulation is mostly unknown. We have investigated TNT formation and its response to treatment in chronic myeloid leukemia (CML) cells with the pathognomonic chimeric fusion kinase BCR-ABL1 after treatment with the tyrosine kinase inhibitor nilotinib and interferon-. Bone marrow cells of chronic phase CML patients and the CML cell line Kcl-22 formed few or no TNTs. Nilotinib and interferon- treatment induced TNT formation in Kcl-22 cells and were found to be linked to increased adherence to fibronectin coated surfaces by restoration of {beta}1-integrin function. This suggests modulation of TNT cell-cell communication in CML as a novel mechanism in kinase inhibitor therapy of CML.