Lymphoblastoid Cell Lines in Pharmacogenomic Discovery and Clinical Translation

Abstract

The ability to predict how an individual patient will respond to a particular treatment is the ambitious goal of personalized medicine. The genetic make up of an individual has been shown to play a role in drug response. For pharmacogenomic studies, human lymphoblastoid cell lines (LCLs) comprise a useful model system for identifying genetic variants associated with pharmacologic phenotypes. The availability of extensive genotype data for many panels of LCLs derived from individuals of diverse ancestry allows for the study of genetic variants contributing to interethnic and interindividual variation in susceptibility to drugs. Many genome-wide association studies for drug-induced phenotypes have been performed in LCLs, often incorporating gene-expression data. LCLs are also being used in follow-up studies to clinical findings to determine how an associated variant functions to affect phenotype. This review describes the most recent pharmacogenomic findings made in LCLs, including the translation of some findings to clinical cohorts.

KEYWORDS::

• β-blockers
• acetaminophen
• chemotherapy
• cytotoxicity
• gene expression
• genome-wide association studies
• HapMap
• immunosuppressants
• lymphoblastoid cell lines
• pharmacogenomics
• radiation
• selective serotonin reuptake inhibitors
• statins

Financial & competing interests disclosure

The authors are supported by the Pharmacogenetics of Anticancer Agents Research Group NIH/National Institute of General Medical Sciences grant U01GM61393, P50 CA125183, CA136765, R21CA139278 and the University of Chicago Cancer Research Center Pilot Funding. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors are supported by the Pharmacogenetics of Anticancer Agents Research Group NIH/National Institute of General Medical Sciences grant U01GM61393, P50 CA125183, CA136765, R21CA139278 and the University of Chicago Cancer Research Center Pilot Funding. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.