Ali Syed Saqib, Raj Ruchika, Kaur Tejinder, Weadick Brenna, Nayak Debasis, No Minnsung, Protos Jane, Odom Hannah, Desai Kajal, Persaud Avinash K, Wang Joanne, Govindarajan Rajgopal
Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Department of Pharmaceutics, College of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Cancers (Basel). 2022 Jun 25;14(13):3113. doi: 10.3390/cancers14133113.
Anticancer nucleoside analogs produce adverse, and at times, dose-limiting hematological toxicities that can compromise treatment efficacy, yet the mechanisms of such toxicities are poorly understood. Recently, cellular nucleoside transport has been implicated in normal blood cell formation with studies from nucleoside transporter-deficient mice providing additional insights into the regulation of mammalian hematopoiesis. Furthermore, several idiopathic human genetic disorders have revealed nucleoside transport as an important component of mammalian hematopoiesis because mutations in individual nucleoside transporter genes are linked to various hematological abnormalities, including anemia. Here, we review recent developments in nucleoside transporters, including their transport characteristics, their role in the regulation of hematopoiesis, and their potential involvement in the occurrence of adverse hematological side effects due to nucleoside drug treatment. Furthermore, we discuss the putative mechanisms by which aberrant nucleoside transport may contribute to hematological abnormalities and identify the knowledge gaps where future research may positively impact treatment outcomes for patients undergoing various nucleoside analog therapies.
抗癌核苷类似物会产生不良的，有时甚至是剂量限制性的血液学毒性，这可能会影响治疗效果，然而，此类毒性的机制却知之甚少。最近，细胞核苷转运与正常血细胞生成有关，对核苷转运体缺陷小鼠的研究为哺乳动物造血的调控提供了更多见解。此外，几种特发性人类遗传疾病已表明核苷转运是哺乳动物造血的重要组成部分，因为单个核苷转运体基因的突变与各种血液学异常有关，包括贫血。在此，我们综述了核苷转运体的最新进展，包括它们的转运特性、在造血调控中的作用以及它们在核苷药物治疗引起的不良血液学副作用发生中的潜在作用。此外，我们讨论了异常核苷转运可能导致血液学异常的推定机制，并确定了知识空白，未来的研究可能会对接受各种核苷类似物治疗的患者的治疗结果产生积极影响。
