Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
SIMT Ospedale San Pietro FBF, Via Cassia, Rome, Italy.
Leuk Res. 2015 Feb;39(2):221-8. doi: 10.1016/j.leukres.2014.11.001. Epub 2014 Nov 18.
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.
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。