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Updated: Mar 17, 2026

Expression of Exogenous Cytokine in Patient-derived Xenografts via Injection with a Cytokine-transduced Stromal Cell Line
Published on: May 10, 2017
PACSIN2 polymorphism is associated with thiopurine-induced hematological toxicity in children with acute
Alenka Smid1, Natasa Karas-Kuzelicki1, Janez Jazbec2
1Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Abstract:
Adequate maintenance therapy for childhood acute lymphoblastic leukemia (ALL), with 6-mercaptopurine as an essential component, is necessary for retaining durable remission. Interruptions or discontinuations of the therapy due to drug-related toxicities, which can be life threatening, may result in an increased risk of relapse. In this retrospective study including 305 paediatric ALL patients undergoing maintenance therapy, we systematically investigated the individual and combined effects of genetic variants of folate pathway enzymes, as well as of polymorphisms in PACSIN2 and ITPA, on drug-induced toxicities by applying a multi-analytical approach including logistic regression (LR), classification and regression tree (CART) and generalized multifactor dimensionality reduction (GMDR). In addition to the TPMT genotype, confirmed to be a major determinant of drug related toxicities, we identified the PACSIN2 rs2413739TT genotype as being a significant risk factor for 6-MP-induced toxicity in wild-type TPMT patients. A gene-gene interaction between MTRR (rs1801394) and MTHFR (rs1801133) was detected by GMDR and proved to have an independent effect on the risk of stomatitis, as shown by LR analysis. To our knowledge, this is the first study showing PACSIN2 genotype association with hematological toxicity in ALL patients undergoing maintenance therapy.
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