IGF1R as druggable target mediating PI3K-δ inhibitor resistance in a murine model of chronic lymphocytic leukemia
With this article in Blood, we just published the results of our very first Illumina next-generation sequencing (NGS) analysis of murine leukemia.
Specifically, our colleagues studied chronic lymphocytic leukemia (CLL) using a murine model of targeted therapy resistance. We were then the ones to sequence the exomes of both resistant and non-resistant cells, searching for DNA mutations responsible for the resistance phenotype. Surprisingly, we could not detect such a mutation. When we subsequently performed RNA sequencing on these same samples, however, we identified distinct gene expression signatures consistently associated with treatment resistance and sensitivity. Notably, these were further validated by our colleagues and even found to be druggable, in vitro and in vivo!
The analysis scripts, which I previously implemented for the analysis of human data, were specifically adapted for this project to work on mouse. They have since been published to github where they are freely available for download, inspection and use. Please also check out Annika Scheffold, who first-authored this work and deserves most of the credit!