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Potential Role of Autophagy Induced by Flt3-Itd and Acid Ceramidase in Acute Myeloid Leukemia Chemo-Resistance: New Insights Publisher Pubmed



Zalpoor H1, 2 ; Bakhtiyari M2, 3 ; Akbari A1, 2 ; Aziziyan F2, 4 ; Shapourian H5 ; Liaghat M2, 6 ; Zarebadie Z7 ; Yahyazadeh S5 ; Tarhriz V8 ; Ganjalikhanihakemi M5
Authors
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Authors Affiliations
  1. 1. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  3. 3. Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  4. 4. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran
  7. 7. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  8. 8. Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Cell Communication and Signaling Published:2022


Abstract

Acute myeloid leukemia (AML) is a type of leukemia with a poor prognosis and survival characterized by abnormal cell proliferation and differentiation. Despite advances in treatment, AML still has a low complete remission rate, particularly in elderly patients, and recurrences are frequently seen even after complete remissions. The major challenge in treating AML is the resistance of leukemia cells to chemotherapy drugs. Thus, to overcome this issue, it can be crucial to conduct new investigations to explore the mechanisms of chemo-resistance in AML and target them. In this review, the potential role of autophagy induced by FLT3-ITD and acid ceramidase in chemo-resistance in AML patients are analyzed. With regard to the high prevalence of FLT3-ITD mutation (about 25% of AML cases) and high level of acid ceramidase in these patients, we hypothesized that both of these factors could lead to chemo-resistance by inducing autophagy. Therefore, pharmacological targeting of autophagy, FLT3-ITD, and acid ceramidase production could be a promising therapeutic approach for such AML patients to overcome chemo-resistance. © 2022, The Author(s).