Megías-Vericat Juan Eduardo, Martínez-Cuadrón David, Solana-Altabella Antonio, Poveda José Luis, Montesinos Pau
Servicio de Farmacia, Área del Medicamento, Hospital Universitario y Politécnico La Fe, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain.
Servicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain.
Pharmaceutics. 2022 Apr 17;14(4):878. doi: 10.3390/pharmaceutics14040878.
Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and ATP-binding cassette family (ABC) pumps. Genetic variability in and could produce interindividual differences in clinical outcomes. A systematic review was performed to evaluate the influence of and polymorphisms and their combinations on efficacy and safety in AML cohorts. Anthracycline intake was especially influenced by polymorphisms, associated with lower hepatic uptake, showing higher survival rates and toxicity in AML studies. The variant alleles of were related to anthracycline intracellular accumulation, increasing complete remission, survival and toxicity. Similar findings have been suggested with and polymorphisms. Polymorphisms of , responsible for cytarabine uptake, demonstrated significant associations with survival and response in Asian populations. Promising results were observed with and combinations regarding anthracycline toxicities. Knowledge of the role of transporter pharmacogenetics could explain the differences observed in drug disposition in the blast. Further studies including novel targeted therapies should be performed to determine the influence of genetic variability to individualize chemotherapy schemes.
急性髓系白血病(AML)原始细胞的抗肿瘤药物摄取可能受流入和流出转运体影响,尤其是溶质载体(SLCs)和ATP结合盒家族(ABC)转运蛋白。[相关基因]的遗传变异可能导致临床结局的个体差异。进行了一项系统评价,以评估[相关基因]多态性及其组合对AML队列疗效和安全性的影响。蒽环类药物的摄取尤其受[相关基因]多态性影响,其与肝脏摄取降低相关,在AML研究中显示出更高的生存率和毒性。[相关基因]的变异等位基因与蒽环类药物细胞内蓄积有关,可提高完全缓解率、生存率并增加毒性。[其他相关基因]多态性也有类似发现。负责阿糖胞苷摄取的[相关基因]多态性在亚洲人群中显示出与生存率和反应显著相关。在蒽环类药物毒性方面,[相关基因]组合显示出有前景的结果。了解转运体药物遗传学的作用可以解释在原始细胞中观察到的药物处置差异。应开展包括新型靶向治疗在内的进一步研究,以确定基因变异对个体化化疗方案的影响。