Characterization of co-transcriptional splicing in acute lymphoblastic leukemia
Alternative splicing is a promising therapeutic target in acute lymphoblastic leukemia. Here, we report the alternative splicing changes in B-ALL cell lines including NALM6 cells and MUTZ-5 cells treated with DYRK1 inhibitor, EHT 1610 and GNF 2133. Dysregulation of co-transcriptional splicing is a therapeutic target in acute lymphoblastic leukemia (ALL). Here, we detected the alternative splicing in NALM6 cells or MUTZ-5 cells treated with EHT 1610 or GNF2133. We detected the alternative splicing in NALM6 cells cells treated with THAL-SNS-032. We also determined the alternative splicing in MEF2D-BCL9 ALL and MEF2D-HNRNPUL1 ALL patient xenografted samples treated with E7820, a anticancer sulfamide, or DMSO. Furthermore, ChIP-seq for RNA polymerase II (Pol II), p-Ser2 Pol II, and p-Ser5 Pol II were performed after DMSO or EHT 1610 treatment in NALM6 cells. ChIP-seq for p-Ser2 Pol II, and p-Ser5 Pol II were performed after DMSO or THAL-SNS-032 treatment in NALM6 cells.PRO-seq in NALM6 cells treated with DMSO, EHT 1610, and THAL-SNS-032 were performed. Overall design: NALM6 and MUTZ-5 cells were treated with 5 µM of EHT 1610 or GNF 2133 following by RNA-seq NALM6 cells were treated with 5 microM of EHT 1610 or DMSO followed by eCLIP-seq for SF3B1 NALM6 cells were treated with 5 microM of EHT 1610 or DMSO followed by ChIP-seq for RNA polymerase II (Pol II), p-Ser2 Pol II, and p-Ser5 Pol II MEF2D-BCL9 and MEF2D-HNRNPUL1 PDX samples were treated with 1 microM of E7820 or DMSO followed by RNA-seq NALM6 cells were treated with, DMSO, 5 microM of EHT 1610, 500 nM of THAL-SNS-032 followed by PRO-seq THAL-SNS-032 treatment (500 nM) in NALM6 cells followed by RNA-seq. NALM6 cells were treated with 500 nM of THAL-SNS-032 or DMSO followed by ChIP-seq for p-Ser2 Pol II and p-Ser5 Pol II.