CONCLUSION

The AML development is a consequence of an accompaniment between genetic, epigenetic and proteomic alterations, causes of specific molecular mechanisms involved in. Nowadays, genetic mutations and cytogenetic alterations are taken into account as markers of great importance for risk stratification and therapeutic decision-making in clinical management. Due to the heterogeneity of mutations in AML, finding a panel of biomarkers would be of more importance for diagnosis, prognosis or monitoring of individual patients, in addition to facilitating individualized-therapeutic decision-making. For example, a panel of integrated biomarkers was recently proposed combining FLT3, NPM1, ERG, CEBPA, and BAALC mutations to place patients into one of the four categories respecting the risks and benefits of proper therapy. Other integrated panels combining ERG, BAALC, WT1, EVI1, MN1 mutations and microRNA expression profiles have been proposed which similarly respecting prognostic factors for risk stratification and therapeutic decision-making. Once an algorithm is established according to these panels, clinical practices can be much closer to achieving personalized medicine and the development of precision medicine. Therefore, identification of mutations and specific biomarkers in each patient and evaluation of the change in methylation signature would contribute to individualized-therapeutic decision-making in AML.5,12,16

Disclosure


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The authors report no conflicts of interest in this work.

References

1. Chiaretti S, Gianfelici V, Ceglie G, Foà R. Genomic characterization of acute leukemias. Med Princ Pract. 2014;23(6):487–506. doi:10.1159/000362793

2. Dohner K, Döhner H. Molecular characterization of acute myeloid leukemia. Haematologica. 2008;93(7):976–982. doi:10.3324/haematol.13345

3. Prada-Arismendy J, Arroyave JC, Röthlisberger S. Molecular biomarkers in acute myeloid leukemia. Blood Rev. 2017;31(1):63–76. doi:10.1016/j.blre.2016.08.005

4. Hekmatimoghaddam S, Jebali A, Dargahi M. Folic acid-functionalized gold and silver nanoparticles: their cytotoxic effect on cancerous myeloid cells with microwave irradiation. Nano Life. 2013;3(2):1350003 (1–6). doi:10.1142/S1793984413500037

5. Gulley ML, Shea TC, Fedoriw Y. Genetic tests to evaluate prognosis and predict therapeutic response in acute myeloid leukemia. J Mol Diagn. 2010;12(1):3–16. doi:10.2353/jmoldx.2010.090054

6. Lagunas-Rangel FA, Chavez-Valencia V, Gomez-Guijosa MA, Cortes-Penagos C. Acute myeloid leukemia-genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res. 2017;11(4):328–339.

7. Masoumi-Dehshiri R, Hashemi AS, Neamatzadeh H, Zare-Zardeini H. a case report: acute myeloid leukemia (FAB M7). Iran J Ped Hematol Oncol. 2014;4(4):188–190.

8. Zaidi SZ, Owaidah T, Al Sharif F, Ahmed SY, Chaudhri N, Aljurf M. The challenge of risk stratification in acute myeloid leukemia with normal karyotype. Hematol Oncol Stem Cell Ther. 2008;1(3):141–158. doi:10.1016/S1658-3876(08)50023-9

9. Haferlach C, Alpermann T, Schnittger S, et al. Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype. Blood. 2012;119(9):2122–2125. doi:10.1182/blood-2011-10-385781

10. Braoudaki M, Tzortzatou-Stathopoulou F. Clinical cytogenetics in pediatric acute leukemia: an update. Clin Lymphoma Myeloma Leuk. 2012;12(4):230–237. doi:10.1016/j.clml.2012.04.004

11. Schlenk RF, Dohner K, Krauter J, et al; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909–1918. doi:10.1056/NEJMoa074306

12. Li Y, Xu Q, Lv N, et al. Clinical implications of genome-wide DNA methylation studies in acute myeloid leukemia. J Hematol Oncol. 2017;10(1):41. doi:10.1186/s13045-017-0409-z

13. Wagner K, Damm F, Gohring G, et al. Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor. J Clin Oncol. 2010;28(14):2356–2364. doi:10.1200/JCO.2009.27.6899

14. Hekmatimoghaddam S, Dehghani Firoozabadi A, Zare-Khormizi MR, Pourrajab F. Sirt1 and Parp1 as epigenome safeguards and microRNAs as SASP-associated signals, in cellular senescence and aging. Ageing Res Rev. 2017;40:120–141. doi:10.1016/j.arr.2017.10.001

15. Mrozek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18(2):115–136. doi:10.1016/S0268-960X(03)00040-7

16. Metzeler KH, Herold T, Rothenberg-Thurley M, AMLCG Study Group; et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128(5):686–698. doi:10.1182/blood-2016-01-693879

17. Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol. 2010;28(16):2739–2747. doi:10.1200/JCO.2009.26.2501

18. Dufour A, Schneider F, Metzeler KH, et al. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol. 2010;28(4):570–577. doi:10.1200/JCO.2008.21.6010

19. Bakshi SR, Brahmbhatt MM, Trivedi PJ, et al. Trisomy 8 in leukemia: A GCRI experience. J Hum Genet. 2012;18(1):106–108.

20. Herold T, Metzeler KH, Vosberg S, et al. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood. 2014;124(8):1304–1311. doi:10.1182/blood-2013-12-540716

21. Knop S, Hebart H, Gratwohl A, et al. Monosomy 7 in myeloid malignancies: parental origin and monitoring by real-time quantitative PCR. Leukemia. 2007;21:1833–1835. doi:10.1038/sj.leu.2404708

22. Sakaguchi M, Yamaguchi H, Najima Y, et al. Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia. Blood Adv. 2018;2(20):2744–2754. doi:10.1182/bloodadvances.2018020305

23. Xu LH, Fang JP, Liu YC, Jones AI, Chai L. Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia. Blood Cancer J. 2020;10(1):1–10. doi:10.1038/s41408-019-0268-7

24. Hollink IHIM, Zwaan CM, Zimmermann M, et al. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia. 2009;23:262–270. doi:10.1038/leu.2008.313

25. Rostamian T, Pourrajab F, Hekmatimoghaddam SH. The effect of 6-thioguanine on proliferation, viability and expression of the genes DNMT 3A, DNMT 3B and HDAC3 in Lymphoid Cancer Cell Line Nalm6. Iran J Ped Hematol Oncol. 2019;10(1):28–37.

26. Suraweera A, O’Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front Onco. 2018;8(92):1–15.

Source: Cancer Management and Research.
Originally published March 25, 2020.


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