Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.

CircRNA: a rising star in leukemia

“…Leukemia can be classified into four main categories, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) ( Bhat et al, 2020 ; Deng, Chao & Zhu, 2023 ; Perez de Acha, Rossi & Gorospe, 2020 ). AML is the most common form of acute leukemia found in adults ( Greiner, Gotz & Wais, 2022 ; Kang et al, 2022 ; Pinto-Merino et al, 2022 ). It is an aggressive and heterogeneous disease characterized by rapid proliferation and arrested differentiation of medulloblastoma in the peripheral blood, bone marrow, and other tissues ( Shapoorian, Zalpoor & Ganjalikhani-Hakemi, 2021 ; Xiang et al, 2022 ).…”

Formulation, Optimization and Evaluation of Cytarabine-Loaded Iron Oxide Nanoparticles: From In Vitro to In Vivo Evaluation of Anticancer Activity

“…This disorder is preceded by cancer cell proliferation, differentiation, migration, and apoptosis abnormalities [ 4 ]. Even though popular therapeutic materials are used to treat cancer and other diseases, nanostructured materials (INPs) have become among the key biomaterials for diagnosing and treating intricate disorders including various contagious diseases and cancers [ 5 ]. Tissue engineering has expanded the spectrum of anticancer therapy as well as offered better compliance to patients [ 6 ].…”

Pharmacogenetics of ABCB1, CDA, DCK, GSTT1, GSTM1 and outcomes in a cohort of pediatric acute myeloid leukemia patients from Colombia

“…Cytidine deaminase (CDA) converts ara-C to the inactive metabolite uracil arabinoside (ara-U), which limits the amount of ara-C to be converted to ara-CTP. 6,[17][18][19] ABCB1, also known as multi-drug resistance protein 1 (MDRP1), is 1 of 49 putative members in the superfamily of human adenosine triphosphate (ATP)-binding cassette (ABC) transporters that encode transporter and channel proteins that function as efflux pumps, 20,21 codifies a P-glycoprotein efflux transporter involved in mediating resistance to several drugs, multidrug resistance phenotype, in cancer 6,18 (Figure S1). Different studies have shown that single nucleotide variants (SNV) in ABCB1, CDA, DCK, GSTT1, and GSTM1 genes are related to drug toxicity in patients with AML.…”

“…Ara‐CTP is a competitor of deoxycytidine 5′‐triphosphate that acts by inhibiting DNA synthesis. Cytidine deaminase ( CDA ) converts ara‐C to the inactive metabolite uracil arabinoside (ara‐U), which limits the amount of ara‐C to be converted to ara‐CTP 6,17–19 . ABCB1 , also known as multi‐drug resistance protein 1 (MDRP1), is 1 of 49 putative members in the superfamily of human adenosine triphosphate (ATP)‐binding cassette (ABC) transporters that encode transporter and channel proteins that function as efflux pumps, 20,21 codifies a P‐glycoprotein efflux transporter involved in mediating resistance to several drugs, multidrug resistance phenotype, in cancer 6,18 (Figure S1).…”