Our study of circular RNA isoforms of the NPM1 gene in acute myeloid leukemia (AML) has just been published to Haematologica!

Alternative splicing generates alternative transcript isoforms of one and the same gene, which may be differentially regulated, carry out distinct functions and contribute to diseases such as cancer. While traditionally studies have focused on linear isoforms only, we set out to study the circular transcriptome of AML in the hopes of identifying disease-specific and -relevant circular RNAs (circRNAs).

We first developed the analysis programs required to identify circRNAs in Illumina RNA sequencing data and then applied these in a systematic analysis of a selected cohort of AML patients. Surprisingly, we actually found an abundant number of circRNAs in these samples and even identified circRNA expression signatures that uniquely characterized healthy vs leukemic and more vs less differentiated cells. We validated several circRNAs identified by our analyses in the wet-lab, including a candidate circRNA of NPM1, which is one of the genes most frequently mutated in AML. With such promising first results, we are excited to continue this work, to extend our cohorts, further develop our in-silico analyses and perform more thorough functional validation and characterization in the lab.

The scripts and NGS data analysis pipelines which I developed for this project have since been published to github where they are freely available for download, inspection and use. Please also check out Susanne Lux, who first-authored this work and deserves most of the credit!