• Treatment Failure in Acute Myeloid Leukemia: Focus on the Role of Extracellular Vesicles
  • Majid Gholizadeh,1 Leila Noorazar,2 Mozhdeh Mohammadian,3 Abbas Hajifathali,4 Ghazaleh Sankanian,5 Elham Roshandel,6,*
    1. 1Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran / 2Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    2. 1Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran / 2Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    3. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    4. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    5. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    6. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


  • Introduction: 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 predisposing 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. In this study, we aim to review the mechanisms that protect the leukemic cells from chemotherapy agents and the roles of leukemia-derived EVs in the induction of drug resistance.
  • Methods: Collecting related articles was performed by Searching keywords including “Acute Myeloblastic Leukemia”, “Drug Resistance”, “Treatment Failure”, “Extracellular Vesicle”, in several databases such as https://scholar.google.com/, https://pubmed.ncbi.nlm.nih.gov/, https://www.scopus.com/. At the next step, similar items were removed and selected articles were classified based on desired sub-titles.
  • Results: Reports showed that malignant cells secrete EVs that transmit messages to adjacent cells and the tumor’s microenvironment. Also, increased secretion of EVs in various malignancies indicates an unfavorable prognostic factor and the possibility of drug resistance. EVs play a potent role in the protection of malignant cells in several ways including transferring of immunosuppressive molecules, microRNA, and organelles by EVs. Also changing in BCL2 family proteins via regulatory factors content in EVs can increase survival of leukemic cells that lead to escape cells from death and result in treatment failure.
  • Conclusion: Numerous studies have highlighted the undeniable role of extracellular vehicles (EVs) in cell-cell communication. Accordingly, EVs can alter the function of target cells by transferring the contents of their origin cell. Recent researches underscore the role of EVs in cancer 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, Treatment Failure, Extracellular Vesicle