Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective

Abstract

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.

Acute therapy-related myelodysplastic syndromes following capecitabine and oxaliplatin therapy in gastric malignant tumor: A case report

“…[16] However, Grade III or IV adverse events in the surgery following capecitabine group were observed mainly in the metastatic breast cancer, including lymphopenia, neutropenia, and thrombocytopenia. [17] A prospective clinical study of gastroenteropancreatic neuroendocrine tumor patients treated with 177Lu-octreotate peptide receptor radionuclide therapy in combination with capecitabine and temozolomide demonstrated that acute toxicity most often affects platelets during the first cycle of treatment. [18] In this case, acute MDS occurred during the early XELOX courses, which was partially relieved by corresponding drug treatment.…”

Association between genetic variants of membrane transporters and the risk of high-grade hematologic adverse events in a cohort of Mexican children with B-cell acute lymphoblastic leukemia

“…Despite the existence of efficient treatment protocols for childhood ALL, 75% of patients experience therapy-related adverse effects, and 5% die from treatment toxicity (3)(4)(5). Among the most frequent side effects are hematologic adverse events leading to immunosuppression and myelosuppression and, consequently, an increased risk of infections (6,7). Moreover, the effects of chemotherapy toxicity lead to treatment modifications or discontinuations which compromise the outcome (8)(9)(10).…”