Treatment Failure in Acute Myeloid Leukemia: Focus on the Role of Extracellular Vesicles

Leuk Res. 2022 Jan:112:106751. doi: 10.1016/j.leukres.2021.106751. Epub 2021 Nov 16.

Abstract

Acute myeloblastic leukemia (AML) is one of the most common types of blood malignancies that results in an AML-associated high mortality rate each year. Several causes have been reported as prognostic factors for AML in children and adults, the most important of which are cytogenetic abnormalities and environmental risk factors. Following the discovery of numerous drugs for AML treatment, leukemic cells sought a way to escape from the cytotoxic effects of chemotherapy drugs, leading to treatment failure. Nowadays, comprehensive studies have looked at the role of extracellular vesicles (EVs) secreted by AML blasts and how the microenvironment of the tumor changes in favor of cancer progression and survival to discover the mechanisms of treatment failure to choose the well-advised treatment. Reports show that malignant cells secrete EVs that transmit messages to adjacent cells and the tumor's microenvironment. By secreting EVs, containing immune-inhibiting cytokines, AML cells inactivate the immune system against malignant cells, thus ensuring their survival. Also, increased secretion of EVs in various malignancies indicates an unfavorable prognostic factor and the possibility of drug resistance. In this study, we briefly reviewed the challenges of treating AML with a glance at the EVs' role in this process. It is hoped that with a deeper understanding of EVs, new therapies will be developed to eliminate the relapse of leukemic cells.

Keywords: Acute myeloblastic leukemia; Drug resistance; Exosome; Extracellular vesicle; Microvesicle; Treatment failure.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Extracellular Vesicles / drug effects*
  • Extracellular Vesicles / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / genetics
  • Treatment Failure
  • Tumor Escape / drug effects*
  • Tumor Escape / genetics
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / genetics

Substances

  • Antineoplastic Agents