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4 results on '"Gupta, Ramneek"'

1. Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia

Author

Tulstrup, Morten, Moriyama, Takaya, Jiang, Chuang, Grosjean, Marie, Nersting, Jacob, Abrahamsson, Jonas, Grell, Kathrine, Hjalgrim, Lisa Lyngsie, Jónsson, Ólafur Gísli, Kanerva, Jukka, Lund, Bendik, Nielsen, Stine Nygaard, Nielsen, Rikke Linnemann, Overgaard, Ulrik, Quist-Paulsen, Petter, Pruunsild, Kaie, Vaitkeviciene, Goda, Wolthers, Benjamin Ole, Zhang, Hui, Gupta, Ramneek, Yang, Jun J., and Schmiegelow, Kjeld

Published
2020
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2. Common Genetic Variants in Trypsin Regulating Genes Are Associated with AsparAginase-Associated Pancreatitis in Children with Acute Lymphoblastic Leukemia: A Ponte Di Legno Toxicity Working Group Study

Author

Wolthers, Benjamin Ole, primary, Frandsen, Thomas Leth, additional, Attarbaschi, Andishe, additional, Barzilai, Shlomit, additional, Colombini, Antonella, additional, Escherich, Gabriele, additional, Grosjean, Marie, additional, Gupta, Ramneek, additional, Liang, Der-Cherng, additional, Moricke, Anja, additional, Patel, Chirag J, additional, Rasmussen, Kirsten K, additional, Samarasinghe, Sujith, additional, Van Der Sluis, Inge M., additional, Stanulla, Martin, additional, Tulstrup, Morten, additional, Zapotocka, Ester, additional, and Schmiegelow, Kjeld, additional

Published
2017
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3. Effects of germline DHFRand FPGSvariants on methotrexate metabolism and relapse of leukemia

Author

Tulstrup, Morten, Moriyama, Takaya, Jiang, Chuang, Grosjean, Marie, Nersting, Jacob, Abrahamsson, Jonas, Grell, Kathrine, Hjalgrim, Lisa Lyngsie, Jónsson, Ólafur Gísli, Kanerva, Jukka, Lund, Bendik, Nielsen, Stine Nygaard, Nielsen, Rikke Linnemann, Overgaard, Ulrik, Quist-Paulsen, Petter, Pruunsild, Kaie, Vaitkeviciene, Goda, Wolthers, Benjamin Ole, Zhang, Hui, Gupta, Ramneek, Yang, Jun J., and Schmiegelow, Kjeld

Abstract

Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P= 1.1 × 10−8) related to suppression of enhancer activity, whereas rs35789560 in FPGS(p.R466C, P= 5.6 × 10−9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGSvariant was linked with increased relapse risk (P= .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.

Published
2020
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