A polymorphism in the 3 '-untranslated region of the NPM1 gene causes illegitimate regulation by microRNA-337-5p and correlates with adverse outcome in acute myeloid leukemia
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摘要Nucleophosmin, encoded by NPM1, is a haploinsufficient suppressor in hematologic malignancies. NPM1 mutations are mostly found in acute myeloid leukemia patients with normal karyotype and associated with favorable prognosis. A polymorphic nucleotide T deletion with unknown significance is present in the NPM1 3'-untranslated region. Here, we showed that the homozygous nucleotide T deletion was associated with adverse outcomes and could independently predict shortened survival in patients with de novo acute myeloid leukemia. Mechanistically, we demonstrated that the nucleotide T deletion created an illegitimate binding NPM1 for miR-337-5p, which was widely expressed in different acute myeloid leukemia subtypes and inhibited NPM1 expression. Accordingly, NPM1 levels were found to be significantly reduced and correlated with miR-337-5p levels in patients carrying a homozygous nucleotide T-deletion genotype. Together, our findings uncover a microRNA-mediated control of NPM1 expression that contributes to disease heterogeneity and suggest additional prognostic values of NPM1 in acute myeloid leukemia.
著者Cheng CK, Kwan TK, Cheung CY, Ng K, Liang P, Cheng SH, Chan NPH, Ip RKL, Wong RSM, Lee V, Li CK, Yip SF, Ng MHL
期刊名稱Haematologica
出版年份2013
月份6
日期1
卷號98
期次6
出版社FERRATA STORTI FOUNDATION
頁次913 - 917
國際標準期刊號0390-6078
語言英式英語
Web of Science 學科類別Hematology

上次更新時間 2021-19-01 於 01:18