Klinisk institutt 2

Midtveisevaluering - Maria Omsland


Abstract: Tunneling nanotube communication in leukemia

Background: The tunneling nanotube (TNT) structure is a newly discovered cell-to-cell communicator found by Rustom et al in 2004. It is a thin (50-200nm in diameter) tunnel- like structure embedded by F-actin and plasma membrane with the possibility to interconnect cells over long distances (from 10-100µm). The biological function of the TNT as well as the molecular machinery responsible for its formation is not yet completely understood. However, TNTs have been found to facilitate intercellular transport of various components such as mitochondria, plasma membrane, bacteria and viruses.

Methods: In the present thesis the goal is to investigate the role of this structure in different blood cancers (leukemia). By investigating multiple leukemias we might be able to dissect some of the functions associated with TNTs. Three different blood cancers have been investigated: acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and adult T-cell leukemia (ATL). These progress differently, where AML is a very heterogeneous leukemia, often caused by different mutations, CML is most often caused by a translocation of chromosome 9 and 22, making the leukemia driving oncogene called Bcr-Abl, ATL is caused by the infection of the human T-leukemia virus type 1 (HTLV-1).

Results: Results from this thesis have so far shown that TNTs are present in different leukemia cells. More specific findings include: the role of TNT in transport of chemotherapeutics between leukemic cells. The NFкB pathway has been suggested to have a functional role in TNT formation in AML and chemotherapeutics used in the clinic has shown to have various effects on TNT formation.  In the CML-TNT study we have investigated the effect of different tyrosine kinase inhibitors (TKIs) on TNT formation in CML cell lines. We are currently studying if the oncogene Bcr-Abl has a function in the TNT formation in this leukemia as well. In the ATL study we have investigated the role of HTLV-1 in the TNT formation and the effect of the chemotherapeutic cytarabine on the regulation of TNTs in ATL.