Blood: Effects of DHFR and FPGS germ cell mutations on methotrexate metabolism and RISK OF ALL recurrence

Methotrexate (MTX) maintenance therapy is critical for the treatment of acute lymphoblastic leukemia (ALL), but achieving appropriate treatment doses with individual differences remains a challenge when configuring the drugTo evaluate genetic factors associated with MTX metabolism, the researchers analyzed 447 ALL cases in the "Nordic Society for Paediatric Haematology and Oncology ALL2008" study and validated it in a separate queue of 196 patientsIt was found that an intergene SNP (rs1382539) located on the original DHFR gene regulation was associated with an increase in levels of short-chain methotrexate glutamate because of its inhibitory activity, while rs35789560 (p.R466C) on FPGS was associated with reduced levels of long-chain methotrexateIn addition, FPGS variation is also associated with an increased risk of ALL recurrenceIn summary, the results of this study reveal the genetic basis of differences in response to methotrexate treatment in ALL patients, or may help improve future drug administration algorithms