Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective.
Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective.
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DOI：
10.3390/cancers14133113
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发表时间：
2022-06-25
期刊：
影响因子：
5.2
通讯作者：
Govindarajan, Rajgopal
中科院分区：
文献类型：
--
作者：
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
抗癌核苷类似物是有希望的治疗方法，但通常会导致破坏性毒性，因此治疗无效。这一机制尚未得到充分研究，但小鼠细胞核苷转运研究可能会提供额外的见解，运输在哺乳动物造血中的作用。细胞核苷转运是哺乳动物造血的一个重要组成部分，这是因为细胞内的突变与血液学异常有关。这篇综述包括核苷转运蛋白，重点是它们的固有特性，造血作用，以及它们在核苷药物治疗副作用中的相互作用。然后，我们提出了潜在的机制来解释核苷转运参与血液疾病。最后，我们指出并倡导未来的研究领域，将改善患者服用核苷类似物治疗的治疗效果。抗癌核苷类似物产生不利的，有时是剂量限制性的血液学毒性，可能会损害治疗效果，但这种毒性的机制知之甚少。最近，细胞核苷转运已涉及正常血细胞的形成，从核苷转运蛋白缺陷小鼠的研究提供了额外的见解哺乳动物造血的调节。此外，几种特发性人类遗传性疾病已经揭示了核苷转运作为哺乳动物造血的重要组成部分，因为单个核苷转运蛋白基因的突变与各种血液学异常（包括贫血）有关。在这里，我们回顾了核苷转运蛋白的最新进展，包括它们的转运特性，它们在造血调控中的作用，以及它们可能参与核苷药物治疗引起的不良血液学副作用的发生。此外，我们还讨论了异常核苷转运可能导致血液学异常的假定机制，并确定了未来研究可能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的知识空白。
Anticancer nucleoside analogs are promising treatments that often result in damaging toxicities and therefore ineffective treatment. Mechanisms of this are not well-researched, but cellular nucleoside transport research in mice might provide additional insight given transport’s role in mammalian hematopoiesis. Cellular nucleoside transport is a notable component of mammalian hematopoiesis due to how mutations within it relate to hematological abnormities. This review encompasses nucleoside transporters, focusing on their inherent properties, hematopoietic role, and their interplay in nucleoside drug treatment side effects. We then propose potential mechanisms to explain nucleoside transport involvement in blood disorders. Finally, we point out and advocate for future research areas that would improve therapeutic outcomes for patients taking nucleoside analog therapies. 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.
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DOI：
10.1080/15257770.2016.1210805
发表时间：
2017-01-02
期刊：
Nucleosides, nucleotides & nucleic acids
影响因子：
--
作者：
Boswell-Casteel RC;Hays FA
通讯作者：
Hays FA
影响因子：
3.2
作者：
Yakabe T;Kitahara K;Komiya K;Sueoka-Aragane N;Kimura S;Sugioka T;Noshiro H
通讯作者：
Noshiro H
DOI：
10.1007/s00259-010-1631-x
发表时间：
2011-02-01
影响因子：
9.1
作者：
Claringbold, Phillip G.;Brayshaw, Paul A.;Turner, J. Harvey
通讯作者：
Turner, J. Harvey
影响因子：
4.8
作者：
Baldwin, SA;Yao, SYM;Young, JD
通讯作者：
Young, JD
影响因子：
20.4
作者：
Arrieta, Oscar;Gallardo-Rincon, Dolores;de la Garza, Jaime
通讯作者：
de la Garza, Jaime