Details

Autor(en) / Beteiligte

• Omsland, Maria
• Andresen, Vibeke
• Gullaksen, Stein-Erik
• Ayuda-Durán, Pilar
• Popa, Mihaela
• Hovland, Randi
• Brendehaug, Atle
• Enserink, Jorrit
• McCormack, Emmet
• Gjertsen, Bjørn Tore

Titel

INTERFERON ALPHA AND TYROSINE KINASE INHIBITORS INCREASE TUNNELING NANOTUBES (TNT) FORMATION AND CELL ADHESION IN CHRONIC MYELIOD LEUKEMIA (CML) CELL LINES

Ist Teil von

• The FASEB journal, 2020-01, Vol.34 (3), p.3773-3791

Erscheinungsjahr

2020

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Chronic myeloid leukemia (CML) is a stem cell disease of the bone marrow where mechanisms of inter-leukemic communication and cell-to-cell interactions are proposed to be important for optimal therapy response. Tunneling nanotubes (TNTs) are novel intercellular communication structures transporting different cargos with potential implications in therapy resistance. Here, we have investigated TNTs in CML cells and following treatment with the highly effective CML therapeutics tyrosine kinase inhibitors (TKIs) and interferon-α (IFNα). CML cells from chronic phase CML patients as well as the blast crisis phase cell lines, Kcl-22 and K562, formed few or no TNTs. Treatment with imatinib increased TNT formation in both Kcl-22 and K562 cells, while nilotinib or interferon-α increased TNTs in Kcl-22 cells only where the TNT increase was associated with adherence to fibronectin-coated surfaces, altered morphology and reduced movement involving β1-integrin. Ex vivo treated cells from chronic phase CML patients showed limited changes in TNT formation similarly to bone marrow cells from healthy individuals. Interestingly, in vivo nilotinib treatment in a Kcl-22 subcutaneous mouse model resulted in morphological changes and TNT-like structures in the tumor-derived Kcl-22 cells. Our results demonstrate that CML cells express low levels of TNTs, but CML therapeutics increase TNT formation in designated cell models indicating TNT functionality in bone marrow derived malignancies and their microenvironment.