Fig. 6

Schematic illustrating the reciprocal interaction between MSCs and ATL cells mediated by ATL-derived exosomes. Exosomes are secreted by ATL cells carrying leukemia-associated genes including Tax, VEGF and miRNAs (miR-21 and -155), in addition to exosome specific genes (TSG-101, CD9 and CD63). Upon delivery of ATL-derived exosomes to MSCs, NF-κB pathway is activated leading to IκB-α phosphorylation and subsequent degradation. The RelA/p50 dimer is now free to translocate into the nucleus and activate cellular events such as proliferation and gene expression of migration (MMP-9 and CXCR4) and angiogenic (VEGF) markers. This in turn supports ATL cells, either by paracrine interaction (soluble factors and exosomes) or by direct cell–cell contact, by creating the right microenvironment that will help ATL cells to proliferate, invade and disseminate to distant sites