The role of exosomes in the stemness maintenance and progression of acute myeloid leukemia

Leukemogenesis occurs in a microenvironment enriched by extracellular microvesicles/exosomes: recent discoveries and questions to be answered

“…Among all leukemia, in particular, the progression of AML is the best-studied hematological malignancy [ 34 , 35 , 37 , 45 ]. Progress of this disorder is affected by (i) ExMVs direct signaling and (ii) phenotype modification.…”

“…These effects are mediated by surface-expressed ligands or the content of fused or internalized inside cargo. Accordingly, ExMVs may (i) interact with cell surface receptors, (ii) fuse with target cells to release their cargo into the cytosol, or (iii) they can be internalized [ 8 , 27 , 29 , 30 , 33 , 34 , 45 ]. The first two mechanisms are the most important, as internalization may lead to lysosomal degradation of ExMVs content.…”

“…Table 1 summarizes several possibilities for how ExMVs may affect the initiation and progression of leukemia. Since ExMVs could be a clinical problem, several strategies have been proposed to eliminate them from circulation [ 8 , 17 , 34 , 45 ]. This will be discussed later by addressing the pros and cons of such developmental therapeutic approaches.…”

“…It also contains many other cells, such as fibroblasts, endothelial cells, and cells lining bone niches, providing signals supporting hematopoiesis. Evidence has accumulated that leukemia cell-derived ExMVs in BM remodel the microenvironment to favor their expansion [ 27 , 34 , 41 , 45 ]. Accordingly, they modify BM hematopoietic stem cell niches, stimulate angiogenesis, and transform BM stroma cells into leukemia-supporting cells.…”

“…1B . As a result of this, it is perturbed, for example, proper retention of normal HSCs in BM niches due to the (i) downregulation of, e.g., stromal-derived factor-1 (SDF-1), kit ligand (KL) and (ii) remodeling of intercellular matrix [ 27 , 29 , 45 ]. This leads to the release of HSCs from their niches.…”