An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment

Abstract

Oxidative stress is associated with several acute and chronic disorders, including hematological malignancies such as acute myeloid leukemia, the most prevalent acute leukemia in adults. Xenobiotics are usually harmless compounds that may be detrimental, such as pharmaceuticals, environmental pollutants, cosmetics, and even food additives. The storage of xenobiotics can serve as a defense mechanism or a means of bioaccumulation, leading to adverse effects. During the absorption, metabolism, and cellular excretion of xenobiotics, three steps may be distinguished: (i) inflow by transporter enzymes, (ii) phases I and II, and (iii) phase III. Phase I enzymes, such as those in the cytochrome P450 superfamily, catalyze the conversion of xenobiotics into more polar compounds, contributing to an elevated acute myeloid leukemia risk. Furthermore, genetic polymorphism influences the variability and susceptibility of related myeloid neoplasms, infant leukemias associated with mixed-lineage leukemia (MLL) gene rearrangements, and a subset of de novo acute myeloid leukemia. Recent research has shown a sustained interest in determining the regulators of cytochrome P450, family 2, subfamily E, member 1 (CYP2E1) expression and activity as an emerging field that requires further investigation in acute myeloid leukemia evolution. Therefore, this review suggests that CYP2E1 and its mutations can be a therapeutic or diagnostic target in acute myeloid leukemia.

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study

“…According to a review, the cytochrome P450 enzyme family is responsible for converting xenobiotics into polar substances, which increases the risk of AML. The study stresses the importance of CYP2E1, a cytochrome P450 member, in the progression of AML, suggesting its potential as a therapeutic and diagnostic target (36). Some studies have explored the fact that CYP2E1 gene variants can indirectly affect bilirubin metabolism.…”

Application of Quantitative Structure-Activity Relationships in the Prediction of New Compounds with Anti-Leukemic Activity

“…The PRMTs have been implicated in human tumorigenesis in numerous studies. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails' arginine [11][12][13]. In human malignancies, elevated PRMT expression is associated with aggressive clinical features and a poor prognosis [10,14].…”