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

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6031
• Main Authors: Sandoval, Cristian, Calle, Yolanda, Godoy, Karina, Farías, Jorge
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.03.2023; MDPI
• Subjects: Acute Disease; Acute myeloid leukemia; Adult; adults; Antimitotic agents; Antineoplastic agents; Bioaccumulation; Bone marrow; Cancer; Cell cycle; Chemotherapy; Cosmetics; cytochrome; Cytochrome P-450 CYP2E1; Cytochrome P450; Cytochromes P450; Disease; Disease susceptibility; DNA methylation; Drug dosages; Enzymes; Epigenetics; Food additives; Gene polymorphism; Genes; Genetic polymorphisms; Genomes; Humans; Infant; Kinases; Leukemia; Leukemia, Myeloid, Acute - genetics; Malignancy; Medical prognosis; Metabolism; Microenvironments; monooxygenase; Mutation; Myeloid-Lymphoid Leukemia Protein - genetics; Neoplasms; Oncology, Experimental; Oxidative stress; Pathophysiology; Polymorphism; polymorphisms; Proteins; Radiation; Remission (Medicine); Review; Sarcoma; Stem cell transplantation; Transcription factors; Tumor Microenvironment; Xenobiotics; Netherlands; cytochrome; polymorphisms; monooxygenase; adults
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076031

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 ( ) 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 ( ) expression and activity as an emerging field that requires further investigation in acute myeloid leukemia evolution. Therefore, this review suggests that and its mutations can be a therapeutic or diagnostic target in acute myeloid leukemia.