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

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

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.

Keywords: Acute myeloid leukemia; Cell differentiation; Leukemia; Membrane antigens; MicroRNA.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • NPM1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • PDCD4 protein, human
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • Nucleophosmin