AI Article Synopsis
- The study assessed the impact of the ABCB1 gene variants on the treatment outcomes and side effects in 522 children with acute lymphoblastic leukemia (ALL).
- The 1199GA variant was associated with a nearly threefold higher relapse risk, while variants 3435CT and 3435TT lowered this risk significantly.
- Additionally, the 3435TT variant was linked to greater bone marrow toxicity during treatment, while the 3435CC variant showed increased liver toxicity after high-dose methotrexate.
Article Abstract
The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P=0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P=0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P<0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT (P=0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G>A may be a new possible predictive marker for outcome in childhood ALL.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762905 | PMC |
| http://dx.doi.org/10.1038/tpj.2014.81 | DOI Listing |
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