Human Lymphoblastoid Cell Lines in Pharmacogenomics

EBV-transformed lymphoblastoid cell lines (LCLs) have been widely used as unlimited genome resources for human genetics. In the post-genome era, the new value of LCLs was created in pharmacogenomic studies, for which genetic information and cellular LCL phenotypes have been exploited in assessing interindividual differences in drug response. The LCL-based model became a powerful tool not only in investigating the global regulatory landscape of gene expression but also in discovering the genetic components underlying individual variation in drug response and the molecular signatures of drug targets. In addition to their utility in forward translational research, LCLs are also useful in reverse translational research, where clinical findings can be validated by functional LCL follow-up studies to understand the mechanism of action in genetic determinants or biomarkers. However, current LCL applications have limitations, including lymphoid tissue specificity and biological noise. Because of potential nongenetic confounders, LCL studies must be replicated in clinical settings with follow-up functional validation studies. Like other genetic materials in current biobanks, LCLs are gradually personified because they can be easily linked to donor health and genetic information. Thus, the LCL-based model can be considered an ex vivo system of the patient or a miniature of the human physiological system under certain conditions. Should more basic studies of LCL biology and its applications be carried out, LCL will become a fundamental element of pharmacogenomic discovery for personalized medicine.