Characterization of RNA-Protein Interaction Networks in Acute Leukemias

Some subtypes of pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) remain very difficult to cure. Thus, despite the effectiveness of conventional chemotherapies, there is still an urgent need to identify new targetable structures and/or pathways. While much is known about transcriptional regulation in leukemias, the post-transcriptional layer remains underexplored. Still, mutations and aberrant expression patterns of some RNA-binding proteins (RBPs) are implicated in leukemogenesis. To reveal further oncogenic RBPs, we performed CRISPR-Cas9 dropout screens targeting 490 RBPs, followed by next generation sequencing. These screens were performed in two AML and ALL cell lines each (NOMO1, 697, M07e, REH), representing either common leukemic subtypes or those associated with poor prognosis. Analysis is currently ongoing, however, we have already identified two promising RBP candidates, namely YBX1 and ZFP36L2, whose pro-proliferative potential was verified experimentally. Next, we will perform functional assays and PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) experiments to elucidate RBP function.

Publikationsverlauf

Artikel online veröffentlicht:
13. Mai 2020