The biological and prognostic role of long non-coding RNA NEAT1 in acute myeloid leukemia

Abstract Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA associated with the promotion of several solid cancers. As part of the FANTOM6 project, we aimed to define its role in acute myeloid leukemia (AML) and myelopoiesis, since it remains largely uninvestigated. We show that NEAT1 expression increases during myelopoiesis, especially in monocytes. NEAT1 expression is elevated in AML compared to normal bone marrow (NBM), especially in AML with inv(16)and t(8;21). In addition, NEAT1 expression correlates positively with ASXL1, KRAS and NRAS mutations, but negatively with TP53 mutant AML. Higher NEAT1 expression is associated with better overall survival in AML, independent of other known risk factors. Knockdown of NEAT1 in AML cells induces monocytic differentiation and upregulated gene expression of genes involved in glucose metabolism. By investigating genome-wide RNA and DNA interactions using RADICL-sequencing, we show that NEAT1 binds to the RUNX2 locus that is associated with differentiation, metabolism, and glucose uptake. The results suggest that the lncRNA NEAT1 has a role in myelopoiesis, AML and is implicated in glycolysis.