Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Los Carreras 753, Osorno 5310431, Chile.
Departamento de Ingeniería Química, Facultad de Ingeniería y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile.
Int J Mol Sci. 2023 Mar 23;24(7):6031. 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.
氧化应激与多种急性和慢性疾病有关，包括血液系统恶性肿瘤，如急性髓系白血病，这是成人中最常见的急性白血病。外源性化学物质通常是无害的化合物，但也可能有害，如药物、环境污染物、化妆品，甚至食品添加剂。外源性化学物质的储存可以作为一种防御机制或生物累积的手段，导致不良影响。在外源性化学物质的吸收、代谢和细胞排泄过程中，可以区分三个步骤：（i）转运酶的流入，（ii）I 相和 II 相，以及（iii）III 相。I 相酶，如细胞色素 P450 超家族中的酶，催化外源性化学物质转化为极性更高的化合物，导致急性髓系白血病风险增加。此外，遗传多态性影响相关髓系肿瘤、与混合谱系白血病基因重排相关的婴儿白血病以及一部分新发急性髓系白血病的可变性和易感性。最近的研究表明，人们持续关注细胞色素 P450 家族 2、亚家族 E、成员 1 的调节剂，作为一个新兴领域，其表达和活性需要进一步研究，以了解急性髓系白血病的演变。因此，本综述认为和其突变可以成为急性髓系白血病的治疗或诊断靶点。
