Role of the Folate-Pathway and the Thymidylate Synthase Genes in Pediatric Acute Lymphoblastic Leukemia Treatment Response
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with a cure rate of approximately 80%. However, despite the generally favorable outcome of ALL treatment, some children relapse or experience severe treatment side effects. Recent research efforts have focused on understanding the patient genetic characteristics that underlie treatment response. To date, several studies have demonstrated that polymorphic genetic variation in genes in the folic acid cycle are associated with altered risks of ALL relapse or treatment toxicity. This chapter summarizes and reviews these results with a particular focus on the methylene tetrahydrofolate and thymidylate synthase genes. While providing intriguing data that germline genetic variation may determine ALL treatment response, adequately powered prospective trials are necessary to translate these findings into clinical practice.
Key WordsAcute lymphoblastic leukemia pharmacogenetics single nucleotide polymorphisms outcome English folate pathway methotrexate
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