PHARMACOGENOMICS AND REGULATION OF APOPTOSIS IN ACUTE MYELOID LEUKAEMIA: MINI REVIEW
Keywords:
AML, pharmacogenomics, ara-C, anthracyclines, apoptosis
Abstract
Acute myeloid leukaemia (AML) is a heterogenous clonal hematopoietic malignancy primarily treated with combination of cytarabine (ara-C) and anthracyclines. Despite high remission rates, especially in younger patients a vast majority of patients die due to relapse or chemotherapy/stem cell transplantation-related toxicity. The partial explanation for this grim clinical outcomelies in the patients¢ genetic variability. In this review we summarize how genetic polymorphisms of proteins in metabolic paths of cytarabine and anthracyclines and proteins involved in regulation of apoptosis influence efficacy and toxicity in the AML treatment.
References
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2. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129(4):424-47.
3. Maksimovic N, Zaric M, Gazibara T, et al. Incidence and Mortality Patterns of Acute Myeloid Leukemia in Belgrade, Serbia (1999–2013). Medicina (Kaunas) 2018;54(1):5.
4. Isidori A, Loscocco F, Curti A, Amadori S, Visani G. Genomic profiling and predicting treatment response in acute myeloid leukemia. Pharmacogenomics. 2019;20(7):467-470.
5. Emadi A, Karp JE. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia. Pharmacogenomics 2012;13(11):1257-69.
6. Mlakar V, Huezo-Diaz Curtis P, Satyanarayana Uppugunduri CR, et al. Pharmacogenomics in Pediatric Oncology: Review of Gene-Drug Associations for Clinical Use. Int J Mol Sci 2016;17(9):1502.
7. Megías-Vericat JE, Montesinos P, Herrero MJ, et al. Pharmacogenomics and the treatment of acute myeloid leukemia. Pharmacogenomics 2016;17(11):1245-72.
8. Lamba JK. Genetic factors influencing cytarabine therapy. Pharmacogenomics 2009; 10(10):1657–74.
9. Wan H, Zhu J, Chen F, et al. SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study. J Exp Clin Cancer Res. 2014;33(1):90.
10. Megías-Vericat JE, Rojas L, Herrero MJ, et al. Influence ofABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: a systematic review and meta-analysis of observational studies. Pharmacogenomics 2015;15:109–118.
11. Lubieniecka JM, Graham J, Heffner D et al. A discoverystudy of daunorubicin induced cardiotoxicity in a sampleof acute myeloid leukemia patients prioritizes P450oxidoreductase polymorphisms as a potential risk factor. Front Genet 2013;4:231.
12. Xiao Q, Deng D, Li H, et al. GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis. Ann Hematol. 2014;93(8):1381-1390.
13. Megias-Vericat JE, Martinez-Cuadron D, Herrero MJ, et al. Pharmacogenetics of Metabolic Genes of Anthracyclines in Acute Myeloid Leukemia. Curr Drug Metab 2018;19(1):55-74.
14. Kulsoom B, Shamsi TS, Afsar NA, et al. Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy? Cancer Manag Res 2018; 10:403-16.
15. Prokop A, Wieder T, Sturn I, et al. Relapse in childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo. Leukemia. 2000;14:1606–1613.
16. Hogarth LA, Hall AG. Increased BAX expression is associated with an increased risk of relapse in childhood acute lymphocytic leukemia. Blood. 1999;93:2671–2678.
17. Köhler T, Schill C, Deininger MW, et al. High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML). Leukemia. 2002;16:22–29.
18. Aref S, Salama O, Al-Tonbary Y, Mansour A. Assessment of bcl-2 expression as modulator of fas mediated apoptosis in acute leukemia. Hematology. 2004;9:113–121.
19. Kornblau SM, Thall PF, Estrov Z, et al. The prognostic impact of BCL2 protein expression in acute myelogenous leukemia varies with cytogenetics. Clin Cancer Res. 1999; 5:1758–1766.
20. Del Poeta G, Venditti A, Del Principe MI, et al. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 2003;101:2125–2131.
21. Guerra VA, DiNardo C, Konopleva M. Venetoclax-based Therapies for Acute Myeloid Leukemia. BestPract Res Clin Haematol. 2019;32(2):145–153.