Glucocorticoid resistance in pediatric leukemia is associated with altered splicing profiles and vulnerability to spliceosome modulation

The aim of the current study is to characterize the global alternative splicing profiles associated with ex vivo GC resistance in pediatric acute lymphoblastic leukemia (ALL). Specifically, we investigated differential splicing profiles in 38 primary childhood ALL samples by using RNA sequencing. Finally, we tested whether GC-resistant cell lines can be sensitized to GC treatment by using the SF3B modulator Pladienolide-B. RNA-sequencing of primary pediatric ALL samples which display different levels of ex-vivo glucocorticoid resistance. RNA-sequencing of leukemia cell lines treated with the spliceosome small-molecule modulator Pladienolide-B.