Principle Investigator: Nathan Salomonis, PhD
While alternative splicing (AS) is a recognized driver in a small percentage of adult acute myeloid leukemias (AML), no known role for AS in pediatric AML currently exists. Through the development of a new computational approach applied to primary patient RNA-sequencing datasets, we discovered that commonly occurring pediatric gene-rearrangements or oncofusions are defined largely by AS.
We will develop a novel advanced computational workflow to identify and prioritize possible therapeutic splicing vulnerabilities in pediatric AML oncofusions. We also will test the requirement of specific implicated splicing regulators on proliferation and splicing regulation in established in vitro models of AML. This work is expected to provide the foundation for developing new precision therapeutics to target splicing pathways in pediatric cancers.