Approches méthodologiques en pharmacogénétique : le modèle des leucémies aiguës lymphoblastiques de l'enfant

Optimisation of anticancer therapeutics allowed reaching remarkable cure rate in childhood acute lymphoblastic leukaemia. However, some patients are resistant to treatment and many develop major complications related to chemotherapy. Recent advances in molecular biology have made possible to highlight the important role of genetics in the development of disease but also in interindividual variability in treatment response. Assessing the impact of genetic polymorphisms by complementary approaches (candidate-gene approach, polygenic model, “whole genome” approach or targeted therapies) confirms the importance of individualized treatment strategies. Thus, several studies on 6-mercaptopurine pharmacogenetics have led to international guidelines for dosage adjustment based on individual genotype. But the use of pharmacogenetic biomarkers in clinical setting is limited in the context of complex polychemotherapy where implementation of a marker alone is insufficient. Currently, larger transfer of pharmacogenetics should include an essential step in validating the therapeutic benefits of genetic testing, expert interpretation of the results achieved in routine, training clinicians to tailor the prescription on the basis of guidelines and aid for the therapeutics.