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Meeting with Hiren

The Spliceosome and CLL SF3B1 Mutations in CLL Rossi et al. Blood. 2011 Dec 22;118(26):6904-8 Wang et al. N Engl J Med. 2011 Dec 29;365(26):2497-506. Quesada et al. Nat Genet. 2011 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.

Induction of Intron retention after FD-895 Treattament in CLL

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

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

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

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

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

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”?