Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia

Gene expression in NPM1 wildtype and mutated AML patients with high or low hsa_circ_0075001 expression In acute myeloid leukemia there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wildtype and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures. AML Patient samples were collected at first diagnosis and chosen from the larger AMLSG_07-04 study cohort (ClinicalTrials.gov identifier: NCT00151242). Mononuclear cells of AML samples were enriched via Ficoll-Hypaque density gradient, and the percentage of leukemic blasts was >85%. For the quantification of hsa_circ_0075001, 44 cytogenetically normal AML cases were selected of which 23 carried an NPM1 mutation.