Role of Chronic Lymphocytic Leukemia (CLL)-Derived Exosomes in Tumor Progression and Survival

Abstract

Chronic lymphocytic leukemia (CLL) is a B-lymphoproliferative disease, which consists of the abnormal proliferation of CD19/CD5/CD20/CD23 positive lymphocytes in blood and lymphoid organs, such as bone marrow, lymph nodes and spleen. The neoplastic transformation and expansion of tumor B cells are commonly recognized as antigen-driven processes, mediated by the interaction of antigens with the B cell receptor (BCR) expressed on the surface of B-lymphocytes. The survival and progression of CLL cells largely depend on the direct interaction of CLL cells with receptors of accessory cells of tumor microenvironment. Recently, much interest has been focused on the role of tumor release of small extracellular vesicles (EVs), named exosomes, which incorporate a wide range of biologically active molecules, particularly microRNAs and proteins, which sustain the tumor growth. Here, we will review the role of CLL-derived exosomes as diagnostic and prognostic biomarkers of the disease.

Keywords: CLL; exosomes; miRNAs.

Figure 1

Exosomes relapse from a primary B cell after stimulation. Both ESCRT-dependent and ESCRT-independent mechanisms of exosomes relapse, require exogenous stimuli on several receptors on B-cell membrane (CD4, BCR, TLR, IL-4R) to start the production and secretion of exosomes. This induces the fusion of the multivesicular bodies (MVBs), containing the exosomes, with the plasma membrane. Via this process, the exosomes containing cytosolic components of parental cell are released into the extracellular compartment and move toward target cells, in which they can modulate different downstream processes.