CRISPRi/a screening to identify functional long non-coding RNAs in pediatric acute myeloid leukemia

Introduction: Long non-coding RNAs (lncRNAs) recently emerged as developmental stage and cell context-specific regulators of gene expression, posing a novel window for targeted therapies in pediatric acute myeloid leukemias (AMLs). Results: We established a microarray-based lncRNA expression atlas for the hematopoietic system including 46 pediatric AML patient samples, and discovered a shared lncRNA signature specific to hematopoietic stem cells (HSCs) and AML blasts. To identify lncRNAs with functions in AML, we first tested CRISPR-Cas9 based transcriptional activator and repressor (CRISPRa/i) systems, and gRNA…