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Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia

Leukemia volume 22, pages 1798–1800 (2008)Cite this article

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Survival rates for ALL have improved dramatically during the past 20 years. The goals of the current trials are to further improve clinical outcome and to minimize side effects.

Treatment with MTX is associated with several side effects in a considerable number of patients, although some patients do not have any side effect at all. MTX-associated mucositis, stomatitis and myelosuppression appear to be related to the folate status of the patient, especially in tissues with high cell turnover. Common polymorphisms have been described in the following folate metabolism-related genes: methionine synthase (MS 2756A>G), methylenetetrahydrofolate reductase (MTHFR 1298A>C and MTHFR 677C>T), methionine synthase reductase (MTRR 66A>G), serine hydroxymethyl transferase (SHMT1 1420C>T), reduced folate carrier (RFC1 80G>A), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A) and TS 28-bp tandem repeats. Figure 1 shows these enzymes to be involved in the various branches of folate metabolism.

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Figure 1
Figure 2

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

    L Huang, W J E Tissing & R Pieters

  2. Department of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    W J E Tissing

  3. Department of Clinical Chemistry, Rotterdam, The Netherlands

    R de Jonge & B D van Zelst

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  1. L Huang
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Correspondence to W J E Tissing.

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Huang, L., Tissing, W., de Jonge, R. et al. Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia 22, 1798–1800 (2008). https://doi.org/10.1038/leu.2008.66

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