Tunneling nanotube (TNT) formation is downregulated by cytarabine and NF-κB inhibition in acute myeloid leukemia (AML)

// Maria Omsland 1 , Oystein Bruserud 2, 3 , Bjorn T. Gjertsen 1, 3 , Vibeke Andresen 1 1 Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway 2 Leukaemia Research Group, Department of Clinical Science, University of Bergen, Bergen, Norway 3 Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway Correspondence to: Bjorn Tore Gjertsen, email: bjorn.gjertsen@uib.no Vibeke Andresen, email: vibeke.andresen@uib.no Keywords: acute myeloid leukemia, tunneling nanotubes, cell-to-cell communication, chemotherapeutics, NF-κB Received: March 29, 2016     Accepted: November 21, 2016     Published: December 10, 2016 ABSTRACT Acute myeloid leukemia (AML) is a bone marrow derived blood cancer where intercellular communication in the leukemic bone marrow participates in disease development, progression and chemoresistance. Tunneling nanotubes (TNTs) are intercellular communication structures involved in transport of cellular contents and pathogens, also demonstrated to play a role in both cell death modulation and chemoresistance. Here we investigated the presence of TNTs by live fluorescent microscopy and identified TNT formation between primary AML cells and in AML cell lines. We found that NF-κB activity was involved in TNT regulation and formation. Cytarabine downregulated TNTs and inhibited NF-κB alone and in combination with daunorubicin, providing additional support for involvement of the NF-κB pathway in TNT formation. Interestingly, daunorubicin was found to localize to lysosomes in TNTs connecting AML cells indicating a novel function of TNTs as drug transporting devices. We conclude that TNT communication could reflect important biological features of AML that may be explored in future therapy development.