miR-21 在 NPM1 突变型急性髓系白血病中过表达。

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias.

机构信息

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

SIMT Ospedale San Pietro FBF, Via Cassia, Rome, Italy.

出版信息

Leuk Res. 2015 Feb;39(2):221-8. doi: 10.1016/j.leukres.2014.11.001. Epub 2014 Nov 18.

DOI:10.1016/j.leukres.2014.11.001

PMID:25543261

Abstract

MicroRNAs (miRs) play a key role in the pathogenesis of human malignancies and particularly in acute myeloid leukemias (AMLs) and are increasingly recognized as potential biomarkers and therapeutic targets. miR-21 is dysregulated in several types of cancers, including some hematologic malignancies, and plays a key role in carcinogenesis, disease recurrence and metastasis. However, no studies have specifically investigated the role of miR-21 in AMLs. In this study we analyzed the expression of miR-21 and of its target PDCD4 (Programmed Cell Death 4) during normal hematopoietic differentiation and in AMLs. Our results showed that: (i) miR-21 expression is strongly up-modulated during normal granulo/monocytic differentiation, while PDCD4 protein level is concomitantly downmodulated; (ii) miR-21 is frequently overexpressed in AML blasts, in association with a marked PDCD4 protein downmodulation; (iii) miR-21 expression level is particularly elevated in NPM1mutant AMLs. Together, these findings suggest that deregulated miR-21 expression may contribute to disease pathogenesis in NPM1-mutated AMLs.

摘要

微小 RNA（miRs）在人类恶性肿瘤的发病机制中起着关键作用，特别是在急性髓系白血病（AMLs）中，并越来越被认为是潜在的生物标志物和治疗靶点。miR-21 在几种类型的癌症中失调，包括一些血液恶性肿瘤，并在致癌作用、疾病复发和转移中发挥关键作用。然而，目前尚无研究专门探讨 miR-21 在 AMLs 中的作用。在这项研究中，我们分析了 miR-21 及其靶基因 PDCD4（程序性细胞死亡 4）在正常造血分化和 AMLs 中的表达。我们的结果表明：（i）miR-21 在正常粒细胞/单核细胞分化过程中表达强烈上调，而 PDCD4 蛋白水平同时下调；（ii）miR-21 在 AML blasts 中频繁过度表达，与 PDCD4 蛋白明显下调相关；（iii）miR-21 的表达水平在 NPM1 突变型 AMLs 中特别升高。综上所述，这些发现表明，miR-21 表达失调可能有助于 NPM1 突变型 AMLs 的发病机制。