In January 2023, a study led by Professor Jianxiang Wang from Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College was published in the international academic journal ——Blood Science . The title of the study is "Effects of genetic polymorphisms on methotrexat levels and toxicity in Chinese patients with acute lymphoblastic leukemia". This study underscores the importance of considering genetic variability in methotrexate (MTX) treatment for acute lymphoblastic leukemia (ALL) patients, particularly in the Chinese population.
Acute lymphoblastic leukemia (ALL) is a hematological malignancy affecting both children and adults, with methotrexate (MTX) being a cornerstone of therapy. However, variability in efficacy and toxicity poses challenges, partly attributed to genetic polymorphisms affecting MTX metabolism.
This study aims to expand understanding of how genetic variables influence MTX pharmacokinetics and toxicities, aiding in personalized treatments for Chinese ALL patients. This study investigates 14 polymorphisms in 6 genes involved in MTX metabolism in 183 Chinese ALL patients. Associations between these genetic variants and MTX serum concentrations and toxicities were analyzed. Significant associations were found in SLCO1B1, SLC19A1, ABCC2, and MTRR genes, suggesting potential utility as predictive biomarkers for MTX-related adverse events in ALL treatment.
The results of the study revealed genetic variants in SLCO1B1 rs4149056 demonstrated associations with elevated serum MTX levels and an increased risk of neutropenia, underscoring the potential utility of this genetic marker in predicting treatment-related toxicities. Similarly, variants in SLC19A1 rs2838958 and rs3788200, as well as MTRR rs1801394, were significantly associated with increased MTX serum concentrations, providing further insights into the genetic determinants of MTX metabolism in the study population.
In conclusion, this study underscores the importance of considering genetic variability in methotrexate (MTX) treatment for acute lymphoblastic leukemia (ALL) patients, particularly in the Chinese population. By employing a retrospective analysis framework and advanced genotyping techniques, we identified significant associations between specific genetic variants and MTX pharmacokinetics and toxicity profiles.
Reference：Hao Q, et al., Wang J, Mi Y.
Effects of genetic polymorphisms on methotrexat levels and toxicity in Chinese patients with acute lymphoblastic leukemia. Blood Science. 5(1):32-38, January 2023.
