1. Meeting with Hiren

2. The Spliceosome and CLL
SF3B1 Mutations in CLL
Rossi et al. Blood Dec 22;118(26):6904-8
Wang et al. N Engl J Med Dec 29;365(26):
Quesada et al. Nat Genet Dec 11;44(1):47-52
Questions :
What is the role of SF3B1 Mutations in CLL
What is the role of Spliceosome Inhibition in CLL
How is the splicing process in NBC vs. CLL and what genes might be involved in abnormal mRNA splicing.

3. Induction of Intron retention after FD-895 Treattament in CLL

4. Induction of Intron retention after FD-895 Treatment in CLL
Relative RNA-seq Read Density

5. FD-895 & Pladienolide B but not Chemotherapy agents Induce Intron Retention (Spliceosome Inhibition) in CLL – (4 hrs)

6. Intron retention (IR) Status in CLL Versus Normal B Cells (NBC)

7. RNAseq Data Acquired via EGA
Ferreira et al . Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia. Genome Research 24:212–226

8. RNAseq data-MATS analysis to be done-Liai et al BMC Cancer

9. Questions to be addressed
What is the status of Intron retention (IR) level between CLL (Leukemic) Vs. Normal B cells?
If there is difference between high risk versus low risk patients based on IGVH mutations (IGVH mutation-low risk, IGVH unmutated-high risk)?
What is the effect of IR on gene expression (GE)
How are the pathways effected between CLL Vs. NBC based IR distributions?
What kind of events involved: intron retention, exon skipping (ES), 3’ or 5”?