Extracellular vesicles (EVs) in acute myeloid leukemia (AML): particles that lead to theleukemia progression

Introduction: Acute myeloid leukemia (AML) is among the most prevalent hematologic malignancies, leadingto significant AML-related mortality annually. This condition arises when immature myeloid blast cells acquiremultiple recurrent genetic and epigenetic alterations, resulting in aberrant proliferation. Recent findings haverevealed that extracellular vesicles (EVs, particles composed of a phospholipid bilayer membrane), or subsetsof them, microvesicles and exosomes, are released from leukemic cells in patients with AML which can elicitvarious effects in these individuals. Microvesicles carry mRNAs and microRNAs that facilitate the transfer ofgenetic information to the target cell, thereby altering its function.Methods: This study was performed by using the collected articles in English that were available on details ofthe main topic in Scopus, PubMed, and Web of Science with keywords extracellular vesicle, microvesicle,exosome, and acute myeloid leukemia, all in title/abstract fieldResults: Tumor-derived extracellular vesicles (EVs) possess the capability to modulate the immune systemthrough the initiation of apoptosis in effector T cells, enhancement of the suppressive function of regulatory Tcells, and inhibition of the activity of natural killer (NK) cells, the latter, hampers the functionality of immunecells, particularly after the decline of NK cell activating receptors (NKG۲D). EVs induce endoplasmic reticulum(ER) stress and the enhancement of the unfolded protein response (UPR) pathway in AML cells and bonemarrow stromal cells, which is recognized for its defensive impact on cancer cells and augmentation of theirresistance to chemotherapy. Moreover, it has been reported that releasing EVs from leukemic cells in drugresistantAML has the capability to interact with monoclonal antibodies present in the bloodstream, therebyimpeding drug accessibility to leukemic cells and inducing drug resistance. The release of miR-۱۵۰ and miR-۱۵۵-enriched exosomes by leukemic cells in AML results in the suppression of differentiation and proliferationof hematopoietic stem/progenitor cells (HSPCs). It has been demonstrated that when stromal cells internalizeexosomes in AML, the induction of Dickkopf Wnt Signaling Pathway Inhibitor ۱ (DKK۱) expression occurs,resulting in the inhibition of regular hematopoiesis and the facilitation of leukemia advancement.Conclusion: The EVs released by AML blasts induce alterations in the tumor microenvironment that promotethe advancement of leukemia through specific mechanisms and as a result, therapeutic interventions will becomeineffective. Hence, further investigations should be conducted to reveal more mechanisms of EVs in AML, sothat the progression of leukemia can be prevented and ultimately successful treatment can be achieved.

کلیدواژه ها:

Extracellular vesicle ، Microvesicle ، Exosome ، Acute Myeloid Leukemia