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NPM1 mutation-modulated microRNA−mRNA regulation in acute myeloid leukemia [miRNA]

ABSTRACT: Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNA−mRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML. Cryopreserved bone marrow cells were obtained from 109 de novo AML patients. Each sample was analyzed with nCounter® Human miRNA Expression Array.

ORGANISM(S): Homo sapiens

SUBMITTER: Wen-Chien Chou 

PROVIDER: E-GEOD-68467 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia.

Chiu Y-C YC   Tsai M-H MH   Chou W-C WC   Liu Y-C YC   Kuo Y-Y YY   Hou H-A HA   Lu T-P TP   Lai L-C LC   Chen Y Y   Tien H-F HF   Chuang E Y EY  

Leukemia 20150916 2

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 systema  ...[more]

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