Long read sequencing to characterize the alternatively spliced transcriptome downstream of mutant JAK3 signalinginT-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a rare cancer that is rapidly fatal without chemotherapy treatment. At present, no personalized therapy is available for the treatment of T-ALL. Fortunately, many of the oncogenes that have been identified in T-ALL can be targeted by existing drugs or by drugs that are currently under development for the treatment of other diseases. Therefore, the treatment of T-ALL patients could potentially be improved by the rational repurposing of existing drugs. For example, JAK kinase inhibitors are being developed for the treatment of auto-immune diseases but are unlikely toshow efficacy for the treatment of T-ALL as single agent. Therefore,more insight in the oncogenic function of the tyrosine kinase mutants can help in the design of novel treatment strategies. This research program is an innovative investigation thataims to understandhow tyrosine kinase mutants cooperate withand regulateother non-oncogenic factors (such as altered splicing events) during T-ALL development. Thisinformation will helpidentify and translate into new avenues for the treatment of T-ALL.