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Blood, 15 July 2005, Vol. 106, No. 2, pp. 717-720. Prepublished online as a Blood First Edition Paper on March 29, 2005; DOI 10.1182/blood-2004-12-4941. This Article Full Text (PDF) Erratum (v106,p1198) All Versions of this Article: 2004-12-4941v1 106/2/717    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Jonge, R. Articles by Lindemans, J. Search for Related Content PubMed PubMed Citation Articles by de Jonge, R. Articles by Lindemans, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 30, 2004 Accepted March 11, 2005 Effect of polymorphisms in folate-related genes on in-vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia Robert de Jonge*, Jan H Hooijberg, Bertrand D van Zelst, Gerrit Jansen, Christina H van Zantwijk, Gert-Jan J Kaspers, Godefridus J Peters, Yaddanapudi Ravindranath, Rob Pieters, and Jan Lindemans Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands Pediatric Oncology/Hematology, Vu University Medical Center, Amsterdam, The Netherlands Rheumatology, Vu University Medical Center, Amsterdam, The Netherlands Medical Oncology, Vu University Medical Center, Amsterdam, The Netherlands Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan, USA Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands * Corresponding author; email: r.dejonge{at}erasmusmc.nl. We studied whether common polymorphisms in genes involved in folate metabolism affect MTX sensitivity. Ex-vivo MTX sensitivity of lymphoblasts obtained from pediatric ALL patients (n=157) was determined by the in-situ thymidylate synthase inhibition assay after either continuous (21-h; TSI50,cont) or short-term (3-h; TSI50,short) MTX exposure. DNA was isolated from lymphoblasts obtained from cytospin slides. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR 677C>T, MTHFR 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC 80G>A) were detected by PCR-RFLP or real-time PCR. Patients with the MTHFR 1298AC variant or the MTRR 66 G-allele showed decreased in-vitro MTX sensitivity measured under both test conditions. SHMT1 1420TT homozygotes only showed decreased MTX sensitivity in the TSI50,cont. In conclusion, polymorphisms in the folate-related genes MTHFR, MTRR, and SHMT1 are related to MTX resistance in pediatric ALL patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. R. Trevino, N. Shimasaki, W. Yang, J. C. Panetta, C. Cheng, D. Pei, D. Chan, A. Sparreboom, K. M. Giacomini, C.-H. Pui, et al. Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects J. Clin. Oncol., December 10, 2009; 27(35): 5972 - 5978. [Abstract] [Full Text] [PDF] R. de Jonge, W. J. E. Tissing, J. H. Hooijberg, G. Jansen, G. J. L. Kaspers, J. Lindemans, G. J. Peters, and R. Pieters Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia Blood, March 5, 2009; 113(10): 2284 - 2289. [Abstract] [Full Text] [PDF] R. R. Almon, E. Yang, W. Lai, I. P. Androulakis, D. C. DuBois, and W. J. Jusko Circadian Variations in Rat Liver Gene Expression: Relationships to Drug Actions J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 700 - 716. [Abstract] [Full Text] [PDF] D. Campana Molecular Determinants of Treatment Response in Acute Lymphoblastic Leukemia Hematology, January 1, 2008; 2008(1): 366 - 373. [Abstract] [Full Text] [PDF] W.-N. Chang, J.-N. Tsai, B.-H. Chen, H.-S. Huang, and T.-F. Fu Serine Hydroxymethyltransferase Isoforms Are Differentially Inhibited by Leucovorin: Characterization and Comparison of Recombinant Zebrafish Serine Hydroxymethyltransferases Drug Metab. Dispos., November 1, 2007; 35(11): 2127 - 2137. [Abstract] [Full Text] [PDF] L. Rosinol, A. Oriol, M. V. Mateos, A. Sureda, P. Garcia-Sanchez, N. Gutierrez, A. Alegre, J. J. Lahuerta, J. de la Rubia, C. Herrero, et al. Phase II Pethema Trial of Alternating Bortezomib and Dexamethasone As Induction Regimen Before Autologous Stem-Cell Transplantation in Younger Patients With Multiple Myeloma: Efficacy and Clinical Implications of Tumor Response Kinetics J. Clin. Oncol., October 1, 2007; 25(28): 4452 - 4458. [Abstract] [Full Text] [PDF] L. Wang, Q. Ke, W. Chen, J. Wang, Y. Tan, Y. Zhou, Z. Hua, W. Ding, J. Niu, J. Shen, et al. Polymorphisms of MTHFD, Plasma Homocysteine Levels, and Risk of Gastric Cancer in a High-Risk Chinese Population Clin. Cancer Res., April 15, 2007; 13(8): 2526 - 2532. [Abstract] [Full Text] [PDF]

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