Targeting SF3B1 in High-Risk B-Cell Acute Lymphoblastic Leukemia

Introduction B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer. The outcomes of young adults with B-ALL are poor, with an event-free survival (EFS) rate of 10 years old, sample#3: relapse), by an MTS assay. In vivo efficacy of Plad-B was tested using an Reh xenograft model and a PDX model. Function of Plad-B was assessed in cell lines by a cell cycle assay, Annexin V assay with flow cytometry, and Western blotting of cleaved PARP and cleaved caspase-3. To determine the changes in the splicing events and apoptosis-associated genes, we are performing RNA-seq at 15min, 30min, 60min, and 24 hours after the treatment. Results SF3B1 mRNA and protein expressions were significantly higher in Reh and JM1 than in hematopoietic monocular cells and CD34-positive HSCs (p < 0.05). SF3B1 protein, but not mRNA, expressions were higher in primary patient samples than in hematopoietic monocular cells and CD34-positive HSCs. There was no significant difference in the mRNA and protein expressions between standard-risk and high-risk groups. Plad-B treatments showed significant cytotoxicity in both Reh and JM1 cell lines with IC50 of 1.2nM and 0.6nM, respectively, at 48 hours after treatment. Plad-B did not show cy