The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?
Abstract
Autophagy is an intracellular self-degradative process that delivers cytoplasmic constituents to the lysosome. Autophagy plays a critical role in balancing sources of energy in response to harsh conditions and nutrient deprivation. Autophagy allows cells to survive in harsh condition and also serve as a death mechanism. Any dysregulation in autophagy signaling may lead to several disorders. Autophagy has been proposed to explain chemotherapy resistance in acute myeloid leukemia (AML). This signaling pathway can either act as a tumor suppressive function or chemo-resistance mechanism. Conventional chemotherapy drugs enhance apoptosis and indicate clinical benefit, but in some cases, relapse and chemotherapy resistance are observed. In leukemia, autophagy may promote cell survival in response to chemotherapy drugs. Therefore, new strategies by inhibiting or activating autophagy may find a broad application for treating leukemia and may significantly enhance clinical outcomes. In this review, we discussed how dimensional role of autophagy in leukemia.
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6. Esclatine A, Chaumorcel M, Codogno P. Macroautophagy signaling and regulation. Curr Top Microbiol Immunol. 2009;335:33-70.
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9. Mizushima N. Autophagy: process and function. Genes Dev. 2007;21(22):2861-73.
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12. Haghi A, Mohammadi S, Heshmati M, et al. Anti-vascular endothelial growth factor effects of sorafenib and arsenic trioxide in acute myeloid leukemia cell lines. Asian Pac J Cancer Prev . 2017;18(6):1655-1661.
13. Kian MM, Mohammadi S, Tavallaei M, et al. Inhibitory effects of arsenic trioxide and thalidomide on angiogenesis and vascular endothelial growth factor expression in leukemia cells. Asian Pac J Cancer Prev. 2018;19(4):1127-1134.
14. Puissant A, Robert G, Auberger P. Targeting autophagy to fight hematopoietic malignancies. Cell Cycle. 2010;9(17):3470-8.
15. Haghi A, Salami M, Kian MM, et al. Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? Cell J. 2020;22(3):253-262.
16. Haghi A, Salami M, Chahardouli B, et al. Arsenic Trioxide and Thalidomide Combination Induces Autophagy Along with Apoptosis in Acute Myeloid Cell Lines. Cell J. 2020;22(2):193-202.
17. Estey EH. Treatment of acute myeloid leukemia. Haematologica. 2009;94(1):10-6.
18. Torgersen ML, Engedal N, Bøe S-O, et al. Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t (8; 21) AML cells. Blood. 2013;122(14):2467-76.
19. Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20(7):1992-2003.
20. Russell RC, Yuan HX, Guan KL. Autophagy regulation by nutrient signaling. Cell Res. 2014;24(1):42-57.
21. Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927-39.
22. Chen Y, Klionsky DJ. The regulation of autophagy–unanswered questions. J Cell SCI. 2011;124(Pt 2):161-70.
23. Levine B, Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol. 2007;7(10):767-77.
24. Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140-56.
25. Ni J, Cozzi P, Hao J, et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736-48.
26. Chang L, Graham P, Hao J, et al. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis. 2014;5(10):e1437.
27. Zhao Y, Yang J, Liao W, et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol. 2010;12(7):665-75.
28. Heath-Engel H, Chang N, Shore G. The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene. 2008;27(50):6419-33.
29. White EJ, Martin V, Liu JL, et al. Autophagy regulation in cancer development and therapy. Am J Cancer Res. 2011;1(3):362-372.
30. Huang JJ, Zhu YJ, Lin TY, et al. Beclin 1 expression predicts favorable clinical outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP. Hum Pathol. 2011;42(10):1459-66.
31. Lindqvist LM, Heinlein M, Huang DC, et al. Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak. Proc Natl Acad Sci U S A. 2014;111(23):8512-7.
32. Marquez RT, Xu L. Bcl-2: Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res. 2012;2(2):214-21.
33. Brech A, Ahlquist T, Lothe RA, et al. Autophagy in tumour suppression and promotion. Mol Oncol. 2009;3(4):366-75.
34. Jang M, Park R, Kim H, et al. AMPK contributes to autophagosome maturation and lysosomal fusion. Sci Rep. 2018;8(1):12637.
35. Moosavi MA, Haghi A, Rahmati M, et al. Phytochemicals as potent modulators of autophagy for cancer therapy. Cancer Lett. 2018;424:46-69.
36. Apel A, Zentgraf H, Büchler MW, et al. Autophagy—A double‐edged sword in oncology. Int J Cancer. 2009;125(5):991-5.
37. White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 2009;15(17):5308-16.
38. Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nat Rev Cancer. 2007;7(12):961-7.
39. Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280-93.
40. Eskelinen EL. The dual role of autophagy in cancer. Curr Opin Pharmacol. 2011;11(4):294-300.
41. Jin S, White E. Role of autophagy in cancer: management of metabolic stress. Autophagy. 2007;3(1):28-31.
42. Kondo Y, Kanzawa T, Sawaya R, et al. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726-34.
43. Shimizu S, Kanaseki T, Mizushima N, et al. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004;6(12):1221-8.
44. Hyttinen JM, Niittykoski M, Salminen A, et al. Maturation of autophagosomes and endosomes: a key role for Rab7. Biochim Biophys Acta. 2013;1833(3):503-10.
45. Wu Q, Deng J, Fan D, et al. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2018;148:64-74.
46. Chollat-Namy M, Safta-Saadoun TB, Haferssas D, et al. The pharmalogical reactivation of p53 function improves breast tumor cell lysis by granzyme B and NK cells through induction of autophagy. Cell Death Dis. 2019;10(10):695.
47. Sachan R, Kundu A, Jeon Y, et al. Afrocyclamin A, a triterpene saponin, induces apoptosis and autophagic cell death via the PI3K/Akt/mTOR pathway in human prostate cancer cells. Phytomedicine. 2018;51:139-50.
48. Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112(12):1809-20.
49. Pyo JO, Jang MH, Kwon YK, et al. Essential roles of Atg5 and FADD in autophagic cell death dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem. 2005;280(21):20722-9.
50. Bommareddy A, Hahm ER, Xiao D, et al. Atg5 Regulates Phenethyl Isothiocyanate–Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells. Cancer Res. 2009;69(8):3704-12.
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| Files | ||
| Issue | Vol 16, No 4 (2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i4.10883 | |
| Keywords | ||
| Autophagy; Acute myeloid leukemia (AML); Cell survival; Chemoresistance | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Haghi A, Mohammadi Kian M, Salemi M, Eghdami MR, Nikbakht M. The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?. Int J Hematol Oncol Stem Cell Res. 2022;16(4):250-263.
