A novel level of regulation of normal and leukemic stem cell hierarchies by differential polyad-enylation of key transcripts (B04)

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Self-renewing hematopoietic stem cells (HSCs) located atop of the hematopoietic system are crucial for the continuous generation of mature cells and also critical for repair in response to injury cues such as infection, inflammation or chemotherapy. Moreover, multipotent HSCs are the cell-of-origin of leu-kemias and leukemic stem cells are likely responsible for relapse after initially successful therapy. Stem cell hierarchies are shaped by a complex array of epigenetic mechanisms including differential methylation, chromatin activity, transcription, translation as well as post-transcriptional and post-translational regulation. Here we address the role of differential polyadenylation of transcripts affecting stability and protein expression in normal HSCs and progenitors and explore whether this mechanism is also operational in leukemic stem cells and therapy resistant leukemic clones.