Extracellular vesicles secreted by leukemic cells as mediators of dysregulated hematopoiesis: acute myeloid leukemia as a case in point

Acute myeloid leukemia (AML) cells exhibit a profound capacity for resistance to conventional chemotherapeutic agents, posing a substantial challenge to existing therapeutic paradigms. Interestingly, this happens in the face of a luxuriant proliferation of leukemic blasts in the peripheral blood. This paradox of concurrent proliferative activity and cellular quiescence underscores a complex biological phenomenon that is intricately mediated by AML-derived Extracellular vesicles (EVs). An extensive literature review search was done on Pubmed/Scopus/Web of Sciences databases to identify studies published between 2013 and 2024 elucidating and demonstrating the effect of AML-derived EVs, Microvesicles (MVs) and Exosomes (Exos) in regulating the normal and dysregulated bone marrow (BM) niche. The review delves into understanding the molecular mechanisms underlying the dual behavior of AML cells - proliferation and quiescence, with a special focus on the role of the EVs and their subtypes viz. Exos and MVs in establishing a discrete BM microenvironment that is subversive to chemotherapy. It offers a novel perspective on the intricate interplay between the leukemic cells and their microenvironment, with implications for therapeutic interventions targeting AML persistence and drug resistance.