Conference Proceedings

A High-Throughput Screening Approach to Identify Therapeutics for the Treatment of Diamond-Blackfan Anaemia

Lorena Nunez Villacis, Sheren J Al-Obaidi, Piyush Madhamshettiwar, Nadine Hein, Jun Chen, Priscilla Soo, Perlita Poh, Megan Pavy, Kaylene J Simpson, Thomas John Gonda, Richard B Pearson, Johan Flygare, Katherine M Hannan, Amee J George, Ross Hannan

Blood | AMER SOC HEMATOLOGY | Published : 2018

Abstract

Abstract Diamond-Blackfan Anaemia (DBA) is a rare blood cell aplasia that presents clinically at approximately 2-3 months of age and its main characteristic is reduced erythroid precursors in the bone marrow, i.e. anemia. Mutations in different ribosomal protein (RP) genes have been associated with DBA, with mutations in RPS19 accounting for 20-25% of all cases. It has been proposed that RPS19 deficiency causes perturbations in ribosome biogenesis, thus activation of the p53-dependent Nucleolar Surveillance Pathway (NSP). In this context free RPs (predominantly L5 and L11) in a complex with 5S rRNA sequester the E3 ubiquitin ligase murine double minute 2 (MDM2), leading to the..

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