Journal article

Genome-wide screening identifies cell cycle control as a synthetic lethal pathway with SRSF2P95H mutation.

Jane Jialu Xu, Alistair M Chalk, Iva Nikolic, Kaylene Simpson, Monique F Smeets, Carl Walkley

Blood Adv | Published : 2021

Abstract

Current strategies to target RNA splicing mutant myeloid cancers proposes targeting the remaining splicing apparatus. This approach has only been modestly sensitizing and is also toxic to non-mutant bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of mis-splicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (AML, MDS, CMML) was performed to identify conserved mis-splicing events. From this analysis, we identified that the cell cycle and DNA repair pathways ..

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