The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood.
Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction.
Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells.
Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.
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The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the NIH. (CA140474 and Clinical and Translational Science Award (CTSA) UL1TR001998); BD was supported by a RISE-DAAD fellowship.
Thurman, Morgan; Van Doorn, Jacob; Danzer, Barbara; Webb, Thomas R.; and Stamm, Stefan, "Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6" (2017). Molecular and Cellular Biochemistry Faculty Publications. 119.