Exosomes derived from chronic myeloid leukemia cells: roles in disease progression, survival, and treatment

Abstract

Exosomes, biologically active extracellular vesicles, are derived from normal and neoplastic cells. Emerging evidence revealed that exosomes modulate cell-cell communication and involve in hemostatic and pathologic processes. Recent studies have shown that exosomes released from cancer cells such as chronic myeloid leukemia cells could act as a key mediator in tumor induction and progression. Myeloid cells-derived exosomes affect different processes including angiogenesis, neoplastic proliferation, tumor cell survival, and imatinib resistance. These exosomes induce angiogenesis and tumor progression by IL-8 overexpression in both leukemic and bone marrow stromal cells. Exosomes cargo could alter the expression of different adhesion molecules, anti-and pro-apoptotic molecules, cytokines, and chemokines such as VCAM-1, ICAM-1, BCL, BAD, BAX, TGF-β, TNF-α, CXCL12 which affect tumor migration, homing, survival, and growth. CML-derived exosomes can also regulate signal transduction pathways, such as ERK/MAPK, ERK/Akt, EGFR/Ras, and Wnt. Furthermore, they can be applied as a vehicle for drug delivery or sensitization of drug-resistant cells. Here, we reviewed the role of chronic myeloid cell-derived exosomes in tumor growth, survival, and resistance to treatment. Keywords: Chronic myeloid leukemia, Exosome, Angiogenesis, Tyrosine kinase inhibitor, Drug resistance