My research project focuses on the role of alternative splicing in high risk pediatric leukemias. Alternative splicing represents a tremendous potential to drive transcriptomic and proteomic diversity, and with that increase cellular and functional complexity in human cells. This flexibility seems especially advantageous for tumor cells, since alterations in splicing are frequently observed in human cancers. In line with this, mutations and/or differential expression of splicing factors have been found in diverse types of adult hematologic malignancies, and dysregulation of splicing has been shown to favor the expression of oncogenic isoforms that contribute to leukemia progression and therapy resistance. However, the mechanisms by which splicing alterations contribute to the development and progression of pediatric leukemia still remains poorly understood. Our aim is to study splicing factor mis-regulation and alternative splicing reprogramming in high risk pediatric leukemia in order to identify “druggable” targets for the development of novel and more adequate therapeutic strategies to fight this devastating disease.
This work is performed in collaboration with prof. dr. Michel Zwaan
(Princess Máxima Center).