Extracellular vesicles in acute myeloid leukemia: The role in disease pathogenesis, potential biomarker, and application in clinical settings
Madhura Chatterjee, Saurabh Gupta, Umesh Kumar, Deepak Parashar, Arindam Maitra, Kaushik Das
Abstract
Acute myeloid leukemia (AML), the most prevalent type of blood cancer, is initiated in the bone marrow and eventually migrates into the blood. It accounts for a 5-year overall survival rate of 29.8 %. AML results from the formation of immature white blood cells, also called AML blasts, from hematopoietic stem cells which eventually give rise to abnormal white blood cells, termed AML cells. The interaction of AML cells with their microenvironment appears to be significantly important in the pathogenesis of AML. A growing body of evidence identifies extracellular vesicles (EVs) to be a key component in intercellular communication via the transfer of biomolecules, such as DNA, RNAs, proteins, non-coding RNAs, lipids, metabolites etc. Although the role of EVs in various solid tumors is well-established, EVs' contribution to the pathogenesis of blood cancer, such as AML remains ill-defined. The present review highlights how EVs promote the progression of AML by influencing leukemogenesis, survival, angiogenesis, chemotherapeutic resistance, and immune evasion. A significant number of EVs are found in the biofluids of AML patients which are shown to carry signature cargo molecules, thereby rendering the EVs as predictive biomarkers for AML pathogenesis. EV-based clinical trials are mentioned in the later part of the review. Finally, EV-based therapeutics and their limitations are also briefly discussed in the context of AML.