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Response to DNA damage and chemoresistance in acute myeloid leukemia: implications of ATM, p53 and C. elegans against cytarabine, cisplatin and etoposide
Introduction Acute myeloid leukemia (AML) is characterized by high genomic instability and elevated relapse rates associated with chemoresistance. The ATM–p53 axis regulates the DNA damage response (DDR), controlling genomic repair, cell cycle arrest, and apoptosis in response to chemotherapeutic agents such as cytarabine, cisplatin, and etoposide. Its dysfunction promotes cell survival and clonal evolution. Caenorhabditis elegans emerges as a conserved experimental model for studying DDR and therapeutic resistance. Objective To analyze the role of the ATM–p53 axis in AML chemoresistance and evaluate the utility of C. elegans as a translational model. Method. Narrative review in PubMed, Scopus, and Google Scholar, prioritizing original articles and reviews from the last 15 years on ATM, p53, AML, DDR, chemoresistance, and C. elegans. Results Alterations in ATM and p53 compromise DDR, favoring apoptosis evasion and activation of compensatory repair and survival pathways, contributing to resistance against cytarabine, cisplatin, and etoposide. C. elegans, through the orthologs atm-1 and cep-1, recapitulates DDR processes and chemoresistance observed in human cells. Conclusion ATM–p53 axis dysfunction is a key determinant of chemoresistance in AML. C. elegans represents a robust platform for identifying conserved molecular vulnerabilities and developing new antileukemic therapeutic strategies.
1. Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol [Internet]. 2023 Mar 1;98(3):502–26. Available from: https://doi.org/10.1002/ajh.26822
2. Pelcovits A, Niroula R. Acute Myeloid Leukemia: A Review. R I Med J (2013). 2020 Apr 1;103:38–40.
3. Long NA, Golla U, Sharma A, Claxton DF. Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications. Stem Cell Rev Rep [Internet]. 2022;18(4):1211–26. Available from: https://doi.org/10.1007/s12015-021-10308-6
4. Zhong S, Kurish H, Walchack R, Li H, Edwards J, Singh A, et al. Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia. Leuk Res [Internet]. 2024 Apr 1 [cited 2025 May 3];139:107468. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0145212624000341
5. Jang JY, Kim D, Im E, Kim ND. Etoposide as a Key Therapeutic Agent in Lung Cancer: Mechanisms, Efficacy, and Emerging Strategies. International Journal of Molecular Sciences 2025, Vol 26, Page 796 [Internet]. 2025 Jan 18 [cited 2025 May 3];26(2):796. Available from: https://www.mdpi.com/1422-0067/26/2/796/htm
6. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, et al. Molecular mechanisms of cisplatin resistance. Oncogene [Internet]. 2012;31(15):1869–83. Available from: https://doi.org/10.1038/onc.2011.384
7. Kryczka J, Kryczka J, Czarnecka-Chrebelska KH, Brzeziańska-Lasota E. Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy. Int J Mol Sci [Internet]. 2021;22(16). Available from: https://www.mdpi.com/1422-0067/22/16/8885
8. Sarin N, Engel F, Kalayda G V, Mannewitz M, Cinatl Jr. J, Rothweiler F, et al. Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest. PLoS One [Internet]. 2017 Jul 26;12(7):e0181081-. Available from: https://doi.org/10.1371/journal.pone.0181081
9. Long X, Gerbing RB, Alonzo TA, Redell MS. Distinct signaling events promote resistance to mitoxantrone and etoposide in pediatric AML: a Children’s Oncology Group report. [cited 2025 May 3]; Available from: www.impactjournals.com/oncotarget
10. Cardona YT, Aparecida M, Morales M. Recibido: noviembre 4 de 2014-Aceptado: enero 30 de. 2015;13(2):95–110.
11. Mueller T, Voigt W, Simon H, Fruehauf A, Bulankin A, Grothey A, et al. Failure of Activation of Caspase-9 Induces a Higher Threshold for Apoptosis and Cisplatin Resistance in Testicular Cancer 1. Cancer Res [Internet]. 2003 [cited 2025 May 3];63:513–21. Available from: http://aacrjournals.org/cancerres/article-pdf/63/2/513/2508443/ch0203000513.pdf
12. Pelcovits A, Niroula R. Acute Myeloid Leukemia: A Review. R I Med J (2013). 2020 Apr 1;103:38–40.
13. Rubnitz JE, Gibson B, Smith FO. Acute Myeloid Leukemia. Hematol Oncol Clin North Am [Internet]. 2010;24(1):35–63. Available from: https://www.sciencedirect.com/science/article/pii/S0889858809002032
14. Venugopal S, Sekeres MA. Contemporary Management of Acute Myeloid Leukemia: A Review. JAMA Oncol [Internet]. 2024 Oct 1;10(10):1417–25. Available from: https://doi.org/10.1001/jamaoncol.2024.2662
15. Debnath A, Nath S. Prognosis and treatment in acute myeloid leukemia: a comprehensive review. Journal of Medical Human Genetics [Internet]. 2024 [cited 2025 May 11];25:91. Available from: https://doi.org/10.1186/s43042-024-00563-w
16. Sossa-Melo C, Abello-Polo V, Salazar LA, Peña AM, Luna-González M, Cuervo-Lozada D, et al. Characteristics, outcomes and treatment patterns in acute myeloid leukemia patients 60 years or older in Colombia: a RENEHOC-PETHEMA study. Ann Hematol [Internet]. 2025;104(1):369–81. Available from: https://doi.org/10.1007/s00277-024-06120-0
17. Cáncer hoy [Internet]. [cited 2025 Sep 12]. Available from: https://gco.iarc.fr/today/en/dataviz/bars-compare-populations?mode=cancer&group_populations=1&cancers=36&populations=903_904
18. Cuenta de Alto Costo (CAC). Leucemias en Colombia, ¿cuál es el panorama de la enfermedad en la población adulta? 2021 Sep 1 [cited 2025 May 3];(segundo informe). Available from: https://cuentadealtocosto.org/cancer/leucemias-en-colombia-cual-es-el-panorama-de-la-enfermedad-en-la-poblacion-adulta/
19. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev [Internet]. 2019;36:70–87. Available from: https://www.sciencedirect.com/science/article/pii/S0268960X18301395
20. National Cancer Institute D. Surveillance, Epidemiology, and End Results Program: Cancer Stat Facts: Leukemia — Acute Myeloid Leukemia (AML). [Internet]. 20020 [cited 2025 May 3]. Available from: https://seer.cancer.gov/statfacts/html/amyl.html
21. Tratamiento de la leucemia mieloide aguda (PDQ®) [Internet]. [cited 2025 May 3]. Available from: https://www.cancer.gov/espanol/tipos/leucemia/pro/tratamiento-lma-adultos-pdq
22. American cancer Society. American Cancer Society. Cancer Facts & Figures. 2025 [cited 2025 May 3]. Cancer Facts & Figures 2025. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2025/2025-cancer-facts-and-figures-acs.pdf
23. Lavin MF, Delia D, Chessa L. ATM and the DNA damage response. EMBO Rep [Internet]. 2005 Feb [cited 2025 Aug 2];7(2):154. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC1369257/
24. Jones MR, Huang JC, Shu ·, Chua Y, Baillie DL, Rose AM. The atm-1 gene is required for genome stability in Caenorhabditis elegans. Mol Genet Genomics [Internet]. 2012 [cited 2025 Aug 2];287:325–35. Available from: http://frodo.wi.mit.edu/primer3/.
25. Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids [Internet]. 2010 [cited 2025 Aug 2];2010:920161. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC2929501/
26. Lee JH, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science (1979) [Internet]. 2005 Apr 22 [cited 2025 Aug 2];308(5721):551–4. Available from: https://pubmed.ncbi.nlm.nih.gov/15790808/
27. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature [Internet]. 2003 Jan 30 [cited 2025 Aug 2];421(6922):499–506. Available from: https://pubmed.ncbi.nlm.nih.gov/12556884/
28. Cusan M, Shen H, Zhang B, Liao A, Yang L, Jin M, et al. SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation. J Clin Invest [Internet]. 2023 Sep 1 [cited 2025 Aug 2];133(17):e163325. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10471171/
29. Lee Y, Rio DC. Mechanisms and regulation of alternative Pre-mRNA splicing. Annu Rev Biochem [Internet]. 2015 Jun 2 [cited 2025 Aug 2];84:291–323. Available from: https://pubmed.ncbi.nlm.nih.gov/25784052/
30. Alonso-Marañón J, Solé L, Álvarez-Villanueva D, Maqueda M, Lobo-Jarne T, Montoto Á, et al. NEMO is essential for directing the kinases IKKα and ATM to the sites of DNA damage HHS Public Access. Sci Signal. 2025;18(877):128.
31. Chen Y, Shao X, Cao J, Zhu H, Yang B, He Q, et al. Phosphorylation regulates cullin-based ubiquitination in tumorigenesis. Acta Pharm Sin B [Internet]. 2020 Feb 1 [cited 2025 Aug 2];11(2):309. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7893081/
32. George B, Kantarjian H, Baran N, Krocker JD, Rios A. TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation. Int J Mol Sci [Internet]. 2021 Oct 1 [cited 2025 Sep 12];22(19):10782. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8509740/
33. Hernández Borrero LJ, El-Deiry WS. Tumor Suppressor p53: Biology, Signaling Pathways, and Therapeutic Targeting. Biochim Biophys Acta Rev Cancer [Internet]. 2021 Aug 1 [cited 2025 Sep 12];1876(1):188556. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8730328/
34. Kamada R, Nomura T, Anderson CW, Sakaguchi K. Cancer-associated p53 Tetramerization Domain Mutants: QUANTITATIVE ANALYSIS REVEALS A LOW THRESHOLD FOR TUMOR SUPPRESSOR INACTIVATION. J Biol Chem [Internet]. 2010 Jan 7 [cited 2025 Sep 12];286(1):252. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3012982/
35. Jeffrey PD, Gorina S, Pavletich NP. Crystal Structure of the Tetramerization Domain of the p53 Tumor Suppressor at 1.7 Angstroms. Science (1979) [Internet]. 1995 Mar 10 [cited 2025 Sep 12];267(5203):1498–502. Available from: /doi/pdf/10.1126/science.7878469
36. Khoury MP, Bourdon JC. p53 Isoforms: An Intracellular Microprocessor? Genes Cancer [Internet]. 2011 Apr [cited 2025 Sep 12];2(4):453. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3135639/
37. Guo Y, Wu H, Wiesmüller L, Chen M. Canonical and non-canonical functions of p53 isoforms: potentiating the complexity of tumor development and therapy resistance. Cell Death Dis [Internet]. 2024 Jun 1 [cited 2025 Sep 12];15(6):1–16. Available from: https://www.nature.com/articles/s41419-024-06783-7
38. Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell [Internet]. 2024 Jun 10 [cited 2025 Sep 12];42(6):946. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11190820/
39. Welch JS. Patterns of mutations in TP53 mutated AML. Best Pract Res Clin Haematol [Internet]. 2018 Dec 1 [cited 2025 Sep 12];31(4):379. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6482955/
40. Fleming S, Tsai XCH, Morris R, Hou HA, Wei AH. TP53 status and impact on AML prognosis within the ELN 2022 risk classification. Blood [Internet]. 2023 Dec 7 [cited 2025 Sep 12];142(23):2029–33. Available from: https://www.sciencedirect.com/science/article/pii/S0006497123021110?via%3Dihub
41. George B, Kantarjian H, Baran N, Krocker JD, Rios A. TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation. Int J Mol Sci [Internet]. 2021 Oct 1 [cited 2025 Sep 12];22(19):10782. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8509740/
42. Welch JS. Patterns of mutations in TP53 mutated AML. Best Pract Res Clin Haematol [Internet]. 2018 Dec 1 [cited 2025 Sep 12];31(4):379. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6482955/
43. Zhao D, Eladl E, Zarif M, Capo-Chichi JM, Schuh A, Atenafu E, et al. Molecular characterization of AML‐MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC‐defining criteria, TP53 allelic state, or TP53 variant allele frequency. Cancer Med [Internet]. 2022 Mar 1 [cited 2025 Sep 12];12(6):6511. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10067127/
44. Shahzad M, Amin MK, Daver NG, Shah MV, Hiwase D, Arber DA, et al. What have we learned about TP53-mutated acute myeloid leukemia? Blood Cancer J [Internet]. 2024 Dec 1 [cited 2025 Sep 12];14(1):202. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11576745/
45. Gold JM, Raja A. Cisplatin. StatPearls [Internet]. 2023 May 22 [cited 2025 May 3]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK547695/
46. Romani AMP. Cisplatin in cancer treatment. Biochem Pharmacol [Internet]. 2022 Dec 1 [cited 2025 May 3];206:115323. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0006295222004178
47. Kiyoi H, Kawashima N, Ishikawa Y. FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development. Cancer Sci [Internet]. 2020 Feb 1;111(2):312–22. Available from: https://doi.org/10.1111/cas.14274
48. Park HJ, Gregory MA, Zaberezhnyy V, Goodspeed A, Jordan CT, Kieft JS, et al. Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation. Henske EP, Rathmell WK, editors. Elife [Internet]. 2022;11:e79940. Available from: https://doi.org/10.7554/eLife.79940
49. Prokocimer M, Molchadsky A, Rotter V. Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy. Blood [Internet]. 2017 Aug 10;130(6):699–712. Available from: https://doi.org/10.1182/blood-2017-02-763086
50. Zhang L, Kathy L. M, David A. S, and List AF. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications. Leuk Lymphoma [Internet]. 2017 Aug 3;58(8):1777–90. Available from: https://doi.org/10.1080/10428194.2016.1266625
51. Faruqi A, Tadi P. Cytarabine. xPharm: The Comprehensive Pharmacology Reference [Internet]. 2023 Aug 8 [cited 2025 Sep 12];1–5. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557680/
52. Su Q, Huang P, Luo X, Zhang P, Li H, Chen Y. Artesunate reverses cytarabine resistance in acute myeloid leukemia by blocking the JAK/STAT3 signaling. Hematology [Internet]. 2023 Dec 31 [cited 2025 Sep 12];28(1). Available from: https://www.tandfonline.com/doi/pdf/10.1080/16078454.2023.2255802
53. Qiu Y, Bai L, Zhao H, Mei X. Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis. BMC Cancer [Internet]. 2024 Dec 1 [cited 2025 Sep 12];24(1):520. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11044605/
54. Sun H, Ren Y, Zhou X, Chen Q, Liu Y, Zhu C, et al. DUSP1 Signaling Pathway Regulates Cytarabine Sensitivity in Acute Myeloid Leukemia. Technol Cancer Res Treat [Internet]. 2023 Jan 1 [cited 2025 Sep 12];22:15330338231207764. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10594969/
55. Sampath D, Cortes J, Estrov Z, Du M, Shi Z, Andreeff M, et al. Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood [Internet]. 2005 Mar 15 [cited 2025 Sep 12];107(6):2517. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC1895741/
56. Sun S, Osterman MD, Li M. Tissue specificity of DNA damage response and tumorigenesis. Cancer Biol Med [Internet]. 2019 Aug 1;16(3):396. Available from: http://www.cancerbiomed.org/content/16/3/396.abstract
57. Podhorecka M, Skladanowski A, Bozko P. H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids [Internet]. 2010 [cited 2025 Nov 11];2010:920161. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC2929501/
58. Sekeres M, Lengle D, Abbey L, Kassack MU, Fischer F, Kurz T, et al. Epigenetic targeting of DNA damage response (DDR)-related mechanisms to overcome acquired cisplatin resistance of tumor cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research [Internet]. 2025 Oct 1 [cited 2025 Jul 29];1872(7):120018. Available from: https://www.sciencedirect.com/science/article/pii/S0167488925001235?via%3Dihub#s0010
59. Jones MR, Huang JC, Chua SY, Baillie DL, Rose AM. The atm-1 gene is required for genome stability in Caenorhabditis elegans. Molecular Genetics and Genomics [Internet]. 2012;287(4):325–35. Available from: https://doi.org/10.1007/s00438-012-0681-0
60. Lee SJ, Gartner A, Hyun M, Ahn B, Koo HS. The Caenorhabditis elegans Werner Syndrome Protein Functions Upstream of ATR and ATM in Response to DNA Replication Inhibition and Double-Strand DNA Breaks. PLoS Genet [Internet]. 2010 Jan [cited 2025 Nov 11];6(1):e1000801. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC2791846/
61. Sossa-Melo C, Abello-Polo V, Salazar LA, Peña AM, Luna-González M, Cuervo-Lozada D, et al. Characteristics, outcomes and treatment patterns in acute myeloid leukemia patients 60 years or older in Colombia: a RENEHOC-PETHEMA study. Ann Hematol [Internet]. 2025;104(1):369–81. Available from: https://doi.org/10.1007/s00277-024-06120-0
62. Sarin N, Engel F, Kalayda G V, Mannewitz M, Cinatl Jr. J, Rothweiler F, et al. Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest. PLoS One [Internet]. 2017 Jul 26;12(7):e0181081-. Available from: https://doi.org/10.1371/journal.pone.0181081
63. Shahzad M, Amin MK, Daver NG, Shah MV, Hiwase D, Arber DA, et al. What have we learned about TP53-mutated acute myeloid leukemia? Blood Cancer J [Internet]. 2024 Dec 1 [cited 2025 Nov 11];14(1):202. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11576745/
64. Fleming S, Tsai XCH, Morris R, Hou HA, Wei AH. TP53 status and impact on AML prognosis within the ELN 2022 risk classification. Blood [Internet]. 2023 Dec 7 [cited 2025 Nov 11];142(23):2029–33. Available from: https://www.sciencedirect.com/science/article/pii/S0006497123021110?via%3Dihub
65. Zhao D, Eladl E, Zarif M, Capo-Chichi JM, Schuh A, Atenafu E, et al. Molecular characterization of AML‐MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC‐defining criteria, TP53 allelic state, or TP53 variant allele frequency. Cancer Med [Internet]. 2022 Mar 1 [cited 2025 Nov 11];12(6):6511. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10067127/
66. Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell [Internet]. 2024 Jun 10 [cited 2025 Nov 11];42(6):946. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11190820/
67. Short NJ, Montalban-Bravo G, Hwang H, Ning J, Franquiz MJ, Kanagal-Shamanna R, et al. Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia. Blood Adv [Internet]. 2020 Nov 24 [cited 2025 Nov 11];4(22):5681. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7686900/
68. Welch JS. Patterns of mutations in TP53 mutated AML. Best Pract Res Clin Haematol [Internet]. 2018 Dec 1 [cited 2025 Nov 11];31(4):379. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6482955/
69. Su Q, Huang P, Luo X, Zhang P, Li H, Chen Y. Artesunate reverses cytarabine resistance in acute myeloid leukemia by blocking the JAK/STAT3 signaling. Hematology (United Kingdom) [Internet]. 2023 Dec 31 [cited 2025 Nov 11];28(1). Available from: https://www.tandfonline.com/doi/pdf/10.1080/16078454.2023.2255802
70. Sampath D, Cortes J, Estrov Z, Du M, Shi Z, Andreeff M, et al. Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood [Internet]. 2005 Mar 15 [cited 2025 Nov 11];107(6):2517. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC1895741/
71. Sun H, Ren Y, Zhou X, Chen Q, Liu Y, Zhu C, et al. DUSP1 Signaling Pathway Regulates Cytarabine Sensitivity in Acute Myeloid Leukemia. Technol Cancer Res Treat [Internet]. 2023 Jan 1 [cited 2025 Nov 11];22:15330338231207764. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10594969/
72. Park HJ, Gregory MA, Zaberezhnyy V, Goodspeed A, Jordan CT, Kieft JS, et al. Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation. Henske EP, Rathmell WK, editors. Elife [Internet]. 2022;11:e79940. Available from: https://doi.org/10.7554/eLife.79940
73. Qiu Y, Bai L, Zhao H, Mei X. Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis. BMC Cancer [Internet]. 2024 Dec 1 [cited 2025 Nov 11];24(1):520. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11044605/
74. Cerón J. Caenorhabditis elegans for research on cancer hallmarks. Dis Model Mech [Internet]. 2023 Jun 1 [cited 2025 Nov 11];16(6):dmm050079. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10259857/
75. Miranda-Vizuete A, Veal EA. Caenorhabditis elegans as a model for understanding ROS function in physiology and disease. Redox Biol [Internet]. 2016 Apr 1 [cited 2025 Nov 11];11:708. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5304259/
76. García-Rodríguez FJ, Martínez-Fernández C, Brena D, Kukhtar D, Serrat X, Nadal E, et al. Genetic and cellular sensitivity of Caenorhabditis elegans to the chemotherapeutic agent cisplatin. Dis Model Mech [Internet]. 2018 Jun 1 [cited 2025 Nov 11];11(6):dmm033506. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6031354/
77. Zhao D, Eladl E, Zarif M, Capo-Chichi JM, Schuh A, Atenafu E, et al. Molecular characterization of AML‐MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC‐defining criteria, TP53 allelic state, or TP53 variant allele frequency. Cancer Med [Internet]. 2022 Mar 1 [cited 2025 Nov 11];12(6):6511. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10067127/
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