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Expert Opinion on Drug Safety Volume 9, 2010 - Issue 1
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Genetic polymorphism of inosine-triphosphate-pyrophosphatase influences mercaptopurine metabolism and toxicity during treatment of acute lymphoblastic leukemia individualized for thiopurine-S-methyl-transferase status

Gabriele Stocco St.Jude Children's Research Hospital, Department of Pharmaceutical Sciences, 262 Danny Thomas Place MS 272, Memphis, TN 38105, USA +1 901 595 3301; +1 901 595 2720; [email protected]; University of Trieste, Department of Life Sciences and Istituto di Ricovero e Cura a Carattere Scientifico “Burlo Garofolo”, Trieste, Italy
,
Kristine R Crews St.Jude Children's Research Hospital, Department of Pharmaceutical Sciences, 262 Danny Thomas Place MS 272, Memphis, TN 38105, USA +1 901 595 3301; +1 901 595 2720; [email protected]
&
William E Evans St.Jude Children's Research Hospital, Department of Pharmaceutical Sciences, 262 Danny Thomas Place MS 272, Memphis, TN 38105, USA +1 901 595 3301; +1 901 595 2720; [email protected]
Pages 23-37 | Published online: 20 Dec 2009

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Boonchai Boonyawat, Chalinee Monsereenusorn, Apichat Photia, Nawachai Lertvivatpong, Varissara Kaewchaivijit, Punyanuch Jindatanmanusan & Piya Rujkijyanont. (2021) ITPA:c.94C>A and NUDT15:c.415C>T Polymorphisms and Their Relation to Mercaptopurine-Related Myelotoxicity in Childhood Leukemia in Thailand. The Application of Clinical Genetics 14, pages 341-351.
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Stéphanie Dulucq, Caroline Laverdière, Daniel Sinnett & Maja Krajinovic. (2014) Pharmacogenetic considerations for acute lymphoblastic leukemia therapies. Expert Opinion on Drug Metabolism & Toxicology 10:5, pages 699-719.
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Nathan D Meeker, Jun J Yang & Joshua D Schiffman. (2010) Pharmacogenomics of pediatric acute lymphoblastic leukemia. Expert Opinion on Pharmacotherapy 11:10, pages 1621-1632.
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Articles from other publishers (42)

Hong-Li Guo, Yue-Tao Zhao, Wei-Jun Wang, Na Dong, Ya-Hui Hu, Yuan-Yuan Zhang, Feng Chen, Li Zhou & Tao Li. (2022) Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising “MINT” sequencing strategy and therapeutic “DNA-TG” monitoring. Frontiers in Pharmacology 13.
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Yeonhong Lee, Eun Jeong Jang, Ha-Young Yoon, Jeong Yee & Hye-Sun Gwak. (2022) Effect of ITPA Polymorphism on Adverse Drug Reactions of 6-Mercaptopurine in Pediatric Patients with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis. Pharmaceuticals 15:4, pages 416.
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Ankita Singh, Harikrishnan Gangadharan, Vikas Gupta, Pradeepta S. Patro, Ramnath Misra & Amita Aggarwal. (2021) Polymorphism of genes involved in methotrexate pathway: Predictors of response to methotrexate therapy in Indian rheumatoid arthritis patients. International Journal of Rheumatic Diseases 24:5, pages 654-662.
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Miriam Saiz‐Rodríguez, Dolores Ochoa, Carmen Belmonte, Manuel Román, Cristina Martínez‐Ingelmo, Lucía Ortega‐Ruíz, Carmen Sarmiento‐Iglesias, Coral Herrador & Francisco Abad‐Santos. (2018) Influence of thiopurine S‐methyltransferase polymorphisms in mercaptopurine pharmacokinetics in healthy volunteers. Basic & Clinical Pharmacology & Toxicology 124:4, pages 449-455.
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Sarah Cargnin, Armando A. Genazzani, Pier Luigi Canonico & Salvatore Terrazzino. (2018) Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis. Pharmacological Research 135, pages 102-111.
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Nikolaos Tsesmetzis, Cynthia Paulin, Sean Rudd & Nikolas Herold. (2018) Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism. Cancers 10:7, pages 240.
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Tina Gerbek, Maria Ebbesen, Jacob Nersting, Thomas L. Frandsen, Malin Lindqvist Appell & Kjeld Schmiegelow. (2018) Role of TPMT and ITPA variants in mercaptopurine disposition. Cancer Chemotherapy and Pharmacology 81:3, pages 579-586.
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Yoichi Kakuta, Yoshitaka Kinouchi & Tooru Shimosegawa. (2017) Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping. Journal of Gastroenterology 53:2, pages 172-180.
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Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin & Roselyne Boulieu. (2017) ITPA Activity in Adults and Children Treated With or Without Azathioprine: Relationship Between TPMT Activity, Thiopurine Metabolites, and Co-medications. Therapeutic Drug Monitoring 39:5, pages 483-491.
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R Franca, P Rebora, N Bertorello, F Fagioli, V Conter, A Biondi, A Colombini, C Micalizzi, M Zecca, R Parasole, F Petruzziello, G Basso, M C Putti, F Locatelli, P d'Adamo, M G Valsecchi, G Decorti & M Rabusin. (2015) Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol. The Pharmacogenomics Journal 17:1, pages 4-10.
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Marzena Skrzypczak-Zielinska, Pawel Borun, Anna Bartkowiak-Kaczmarek, Oliwia Zakerska-Banaszak, Michal Walczak, Agnieszka Dobrowolska, Mateusz Kurzawski, Malgorzata Waszak, Daniel Lipinski, Andrzej Plawski & Ryszard Slomski. (2016) A Simple Method for TPMT and ITPA Genotyping Using Multiplex HRMA for Patients Treated with Thiopurine Drugs. Molecular Diagnosis & Therapy 20:5, pages 493-499.
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Mehmet Coskun, Casper Steenholdt, Nanne K. de Boer & Ole Haagen Nielsen. (2015) Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease. Clinical Pharmacokinetics 55:3, pages 257-274.
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T. Adam de Beaumais, A. Baruchel & E. Jacqz-Aigrain. (2015) Approches méthodologiques en pharmacogénétique : le modèle des leucémies aiguës lymphoblastiques de l’enfant. Revue d'Oncologie Hématologie Pédiatrique 3:4, pages 215-220.
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Fatemeh Azimi, Yousef Mortazavi, Samin Alavi, Mitra Khalili & Ali Ramazani. (2015) Frequency of ITPA gene polymorphisms in Iranian patients with acute lymphoblastic leukemia and prediction of its myelosuppressive effects. Leukemia Research 39:10, pages 1048-1054.
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Ryoko Suzuki, Hiroko Fukushima, Emiko Noguchi, Masahiro Tsuchida, Nobutaka Kiyokawa, Kazutoshi Koike, Enbo Ma, Hideto Takahashi, Chie Kobayashi, Ryoko Nakajima-Yamaguchi, Aiko Sakai, Makoto Saito, Atsushi Iwabuchi, Keisuke Kato, Tomohei Nakao, Ai Yoshimi, Ryo Sumazaki & Takashi Fukushima. (2015) Influence of SLCO1B1 polymorphism on maintenance therapy for childhood leukemia . Pediatrics International 57:4, pages 572-577.
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Lin Mei, Evelena P. Ontiveros, Elizabeth A. Griffiths, James E. Thompson, Eunice S. Wang & Meir Wetzler. (2015) Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy. Blood Reviews 29:4, pages 243-249.
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Phuong Thu Vu Hoang, Jérôme Ambroise, Anne-France Dekairelle, Jean-François Durant, Valentina Butoescu, Vu Luan Dang Chi, Nghia Huynh, Tan Binh Nguyen, Annie Robert, Christiane Vermylen & Jean-Luc Gala. (2015) Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?. British Journal of Clinical Pharmacology 79:3, pages 429-440.
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Mauricio J Farfan, Carolina Salas, Cristina Canales, Felipe Silva, Milena Villarroel, Katherine Kopp, Juan P Torres, María E Santolaya & Jorge Morales. (2014) Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia. BMC Cancer 14:1.
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Ping LiQuan ChenYa-Di WangMin-Wen Ha. (2014) Effects of MTHFR Genetic Polymorphisms on Toxicity and Clinical Response of Irinotecan-Based Chemotherapy in Patients with Colorectal Cancer . Genetic Testing and Molecular Biomarkers 18:5, pages 313-322.
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Gabriele Stocco, Eva Cuzzoni, Sara De Iudicibus, Raffaella Franca, Diego Favretto, Noelia Malusà, Margherita Londero, Gabriele Cont, Fiora Bartoli, Stefano Martelossi, Alessandro Ventura & Giuliana Decorti. (2014) Deletion of Glutathione-S-Transferase M1 Reduces Azathioprine Metabolite Concentrations in Young Patients With Inflammatory Bowel Disease. Journal of Clinical Gastroenterology 48:1, pages 43-51.
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Nicholas C. Dracopoli & Katie Streicher. 2014. Genomic Biomarkers for Pharmaceutical Development. Genomic Biomarkers for Pharmaceutical Development 23 49 .
Peter D. Simone, Youri I. Pavlov & Gloria E.O. Borgstahl. (2013) ITPA (inosine triphosphate pyrophosphatase): From surveillance of nucleotide pools to human disease and pharmacogenetics. Mutation Research/Reviews in Mutation Research 753:2, pages 131-146.
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Hazhar Karim, Aram Ghalali, Pierre Lafolie, Sigurd Vitols & Alan K. Fotoohi. (2013) Differential role of thiopurine methyltransferase in the cytotoxic effects of 6-mercaptopurine and 6-thioguanine on human leukemia cells. Biochemical and Biophysical Research Communications 437:2, pages 280-286.
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Adele Corrigan, Monica Arenas-Hernandez, Paul Blaker, Jeremy Sanderson & Anthony Marinaki. (2012) Let’s get personal: predicting thiopurine and fluoropyrimidine toxicity. Personalized Medicine 9:8, pages 859-870.
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Paul Andrew BlakerMonica Arenas-Hernandez, Anthony Marin Marinaki & Jeremy David Sanderson. (2012) The pharmacogenetic basis of individual variation in thiopurine metabolism. Personalized Medicine 9:7, pages 707-725.
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Steven W. Paugh, Mary V. Relling & William E. Evans. 2013. Childhood Leukemias. Childhood Leukemias 309 331 .
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Daniel CronaFederico Innocenti. (2012) Can knowledge of germline markers of toxicity optimize dosing and efficacy of cancer therapy?. Biomarkers in Medicine 6:3, pages 349-362.
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Navin Pinto, Susan L. Cohn & M. Eileen Dolan. (2012) Using Germline Genomics to Individualize Pediatric Cancer Treatments. Clinical Cancer Research 18:10, pages 2791-2800.
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Yoichi Tanaka, Atsushi Manabe, Hisaya Nakadate, Kensuke Kondoh, Kozue Nakamura, Katsuyoshi Koh, Tomoyuki Utano, Akira Kikuchi & Takako Komiyama. (2012) The activity of the inosine triphosphate pyrophosphatase affects toxicity of 6-mercaptopurine during maintenance therapy for acute lymphoblastic leukemia in Japanese children. Leukemia Research 36:5, pages 560-564.
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Bo PangJose L. McFalineNicholas E. Burgis, Min DongKoli Taghizadeh, Matthew R. SullivanC. Eric ElmquistRichard P. Cunningham & Peter C. Dedon. (2012) Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA. Proceedings of the National Academy of Sciences 109:7, pages 2319-2324.
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Ute Hofmann, Georg Heinkele, Sieglinde Angelberger, Elke Schaeffeler, Cornelia Lichtenberger, Simon Jaeger, Walter Reinisch & Matthias Schwab. (2012) Simultaneous Quantification of Eleven Thiopurine Nucleotides by Liquid Chromatography-Tandem Mass Spectrometry. Analytical Chemistry 84:3, pages 1294-1301.
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L. Chouchana, C. Narjoz, P. Beaune, M.‐A. Loriot & X. Roblin. (2011) Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 35:1, pages 15-36.
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S W Paugh, G Stocco, J R McCorkle, B Diouf, K R Crews & W E Evans. (2011) Cancer Pharmacogenomics. Clinical Pharmacology & Therapeutics 90:3, pages 461-466.
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Hans-Georg Eichler, Eric Abadie, Alasdair Breckenridge, Bruno Flamion, Lars L. Gustafsson, Hubert Leufkens, Malcolm Rowland, Christian K. Schneider & Brigitte Bloechl-Daum. (2011) Bridging the efficacy–effectiveness gap: a regulator's perspective on addressing variability of drug response. Nature Reviews Drug Discovery 10:7, pages 495-506.
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Hazhar Karim, Jamileh Hashemi, Catharina Larsson, Ali Moshfegh, Alan K. Fotoohi & Freidoun Albertioni. (2011) The pattern of gene expression and gene dose profiles of 6-Mercaptopurine- and 6-Thioguanine-resistant human leukemia cells. Biochemical and Biophysical Research Communications 411:1, pages 156-161.
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Valery Elie, Tiphaine de Beaumais, May Fakhoury & Evelyne Jacqz-Aigrain. (2011) Pharmacogenetics and individualized therapy in children: immunosuppressants, antidepressants, anticancer and anti-inflammatory drugs. Pharmacogenomics 12:6, pages 827-843.
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S. Ngo, G. Sauvetre, O. Vittecoq, H. Lévesque & I. Marie. (2011) Aplasie médullaire induite par l’azathioprine : intérêt de la recherche systématique d’une mutation du gène de la thiopurine S-méthyltransférase ?. La Revue de Médecine Interne 32:6, pages 373-376.
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Seyhan Yağar, Soner Yavaş & Bensu Karahalil. (2010) The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery. Molecular Biology Reports 38:5, pages 3383-3389.
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Tiphaine Adam de Beaumais, May Fakhoury, Yves Medard, Said Azougagh, Daolun Zhang, Karima Yakouben & Evelyne Jacqz-Aigrain. (2011) Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy. British Journal of Clinical Pharmacology 71:4, pages 575-584.
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Cynthia A. Prows. (2011) Infusion of Pharmacogenetics Into Cancer Care. Seminars in Oncology Nursing 27:1, pages 45-53.
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Steven W Paugh, Gabriele Stocco & William E Evans. (2010) Pharmacogenomics in pediatric leukemia. Current Opinion in Pediatrics 22:6, pages 703-710.
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