Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

 Proteome changes that drive acute myeloid leukemia patients to relapse  (#566)

Maria Hernandez-Valladares 1 2 , Elise Aasebø 1 , Frode Berven 3 , Frode Selheim 3 , Øystein Bruserud 1
  1. Clinical Sciences, University of Bergen, Bergen, Hordaland, Norway
  2. University of Sydney, Camperdown, NSW, Australia
  3. Biomedicine, University of Bergen, Bergen, Hordaland, Norway

Acute myeloid leukemia (AML) is a hematological cancer that affects mainly the elderly and infants. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Therefore, understanding of the biological factors that determine relapse has become a major interest in clinical AML. In order to identify the proteins and their phosphorylated modifications involved in AML relapse, we performed a global proteome and phosphoproteome study by liquid chromatography mass spectrometry (LC-MS) with  primary cells from 41 AML patients at time of diagnosis that were defined as RELAPSE or REL_FREE according to their relapse status after a 5-year clinical follow-up post diagnosis. Our findings show that RNA processing and V-ATP-ases proteins along with CDKs and CSK2 activities are increased in patients that will relapse. MS-based results were further validated with cell proliferation assays using bafilomycin A1, CX-4945, abemaciclib and SNS-032 inhibitors. Moreover, proteomics studies with eight matched diagnosis-relapse AML samples showed the persistent activities of RNA processing and DNA repair factors during relapse and uncovered the drug targetability of mitochondrial protein synthesis in resistant AML blasts. Our study presents molecules that could predict AML relapse and direct new therapeutic strategies that might circumvent more aggressive AML episodes.