Crosstalk between CML cells with HUVECS and BMSCs through CML derived exosomes.

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by presence of the BCR-ABL fusion gene which encodes the constitutively active BCR-ABL chimeric protein. Imatinib is first FDA approved first-line BCR-ABL targeting drug for the treatment of newly diagnosed CML cases. Nowadays there are recently developed and more efficient TKIs in the market. Despite the improvements in the CML therapy by using tyrosine kinase inhibitors (TKIs) primary/secondary resistance or progression from chronic to accelerated and blastic phase may be developed in some cases. Underlying mechanisms of TKI resistance and disease progression may results from BCR/ABL dependent or independent alterations. Recently it was revealed that tumor microenvironment is very important for cancer cell growth, survival, proliferation, hemostasis, invasion and metastasis. Exosomes derived from tumor cells contain many important signaling molecules and transfer these molecules in the neighbouring cells. In the bone marrow matrix CML cells, CML leukemic stem cells,cells, bone marrow mesenchymal stromal cells can communicate with each other through exosomes. In this review we focused on biological and clinical importance of CML derived exosomes and we will summarize the recent studies in this field.