[Application of genome editing technology for the validation of pharmacogenomics in acute lymphoblastic leukemia]

Therapeutic outcome in childhood acute lymphocytic leukemia has been dramatically improved by recent developments in treatment. However, disease relapse is still observed in approximately 10-15% of the patients. Moreover, adverse effects associated with intensified chemotherapy and hematopoietic stem cell transplantation remain important clinical issues for some survivors. Personalized medicine is valuable, under these circumstances, to reduce adverse effects and further improve the therapeutic outcome. Thus, identifying pharmacogenomic backgrounds associated with individual variation in drug sensitivity of leukemia cells and chemotherapy-induced adverse effects is important for precision medicine development. Recent advances in genome-editing technologies, such as CRISPR/Cas9 system, enable direct confirmation of associations between drug sensitivities and genetic backgrounds, such as polymorphisms and mutations, in the intrinsic genes of leukemia cells. Consequently, genome-editing systems are an ideal tool to develop in vitro and in vivo experimental models of drug sensitivity or resistance. The usefulness of the CRISPR/Cas9 system for the validation of pharmacogenomics in the selection of chemotherapeutic agents for acute lymphocytic leukemia has been discussed with specific examples in this review.