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9 results on '"Smith, Colton"'

2. Class II Human Leukocyte Antigen Variants Associate With Risk of Pegaspargase Hypersensitivity

Author

Liu, Yiwei, primary, Yang, Wenjian, additional, Smith, Colton A., additional, Cheng, Cheng, additional, Karol, Seth E., additional, Larsen, Eric C., additional, Winick, Naomi, additional, Carroll, William L., additional, Loh, Mignon L., additional, Raetz, Elizabeth A., additional, Hunger, Stephen P., additional, Winter, Stuart S., additional, Dunsmore, Kimberly P., additional, Devidas, Meenakshi, additional, Yang, Jun J., additional, Evans, William E., additional, Jeha, Sima, additional, Pui, Ching‐Hon, additional, Inaba, Hiroto, additional, and Relling, Mary V., additional

Published
2021
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3. Effects of NT5C2 Germline Variants on 6‐Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia

Author

Jiang, Chuang, primary, Yang, Wenjian, additional, Moriyama, Takaya, additional, Liu, Chengcheng, additional, Smith, Colton, additional, Yang, Wentao, additional, Qian, Maoxiang, additional, Li, Ziping, additional, Tulstrup, Morten, additional, Schmiegelow, Kjeld, additional, Crews, Kristine R., additional, Zhang, Hui, additional, Pui, Ching‐Hon, additional, Evans, William, additional, Relling, Mary, additional, Bhatia, Smita, additional, and Yang, Jun J., additional

Published
2020
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4. Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia

Author

Finch, Emily R., primary, Smith, Colton A., additional, Yang, Wenjian, additional, Liu, Yiwei, additional, Kornegay, Nancy M., additional, Panetta, John C., additional, Crews, Kristine R., additional, Molinelli, Alejandro R., additional, Cheng, Cheng, additional, Pei, Deqing, additional, Ramsey, Laura B., additional, Karol, Seth E., additional, Inaba, Hiroto, additional, Sandlund, John T., additional, Metzger, Monika, additional, Evans, William E., additional, Jeha, Sima, additional, Pui, Ching‐Hon, additional, and Relling, Mary V., additional

Published
2019
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6. Palmar-plantar erythrodysesthesia syndrome following treatment with high-dose methotrexate or high-dose cytarabine

Author

Karol, Seth E., primary, Yang, Wenjian, additional, Smith, Colton, additional, Cheng, Cheng, additional, Stewart, Clinton F., additional, Baker, Sharyn D., additional, Sandlund, John T., additional, Rubnitz, Jeffrey E., additional, Bishop, Michael W., additional, Pappo, Alberto S., additional, Jeha, Sima, additional, Pui, Ching-Hon, additional, and Relling, Mary V., additional

Published
2017
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9. Effects of NT5C2 Germline Variants on 6-Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia.

Author

Jiang C, Yang W, Moriyama T, Liu C, Smith C, Yang W, Qian M, Li Z, Tulstrup M, Schmiegelow K, Crews KR, Zhang H, Pui CH, Evans W, Relling M, Bhatia S, and Yang JJ

Subjects
Adolescent, Alleles, Child, Child, Preschool, Cohort Studies, Erythrocytes metabolism, Female, Gene Expression Regulation, Neoplastic genetics, Genome-Wide Association Study, Germ-Line Mutation, Humans, Linkage Disequilibrium, Male, Multigene Family, Multivariate Analysis, Mutation, Missense, Polymorphism, Single Nucleotide, Thioguanine blood, Young Adult, 5'-Nucleotidase genetics, Antimetabolites, Antineoplastic pharmacokinetics, Mercaptopurine pharmacokinetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism
Abstract

6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide (TGN) metabolites. A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing of NT5C2 in 588 children with ALL and identified 121 single nucleotide polymorphisms nominally associated with erythrocyte TGN during 6-MP treatment (P < 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6-MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in-cis. Our results indicated that NT5C2 germline variation significantly contributes to interpatient variability in thiopurine drug disposition., (© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Published
2021
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