Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia
Journal
Leukemia
Journal Volume
30
Journal Issue
2
Pages
274-284
Date Issued
2016
Author(s)
Chiu Y.-C.
Liu Y.-C.
Kuo Y.-Y.
Chen Y.
Abstract
Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML. ? 2016 Macmillan Publishers Limited.
SDGs
Other Subjects
messenger RNA; microRNA; messenger RNA; microRNA; nuclear protein; nucleophosmin; acute myeloblastic leukemia; Article; cancer prognosis; cancer survival; controlled study; gene; gene mutation; human; human cell; major clinical study; microarray analysis; mutant; NPM1 gene; priority journal; acute myeloblastic leukemia; genetics; mortality; mutation; prognosis; tumor cell line; Cell Line, Tumor; Humans; Leukemia, Myeloid, Acute; MicroRNAs; Mutation; Nuclear Proteins; Prognosis; RNA, Messenger
Publisher
Nature Publishing Group
Type
journal article