Deregulation of miR-1, miR486, and let-7a in cytogenetically normal acute myeloid leukemia: association with NPM1 and FLT3 mutation and clinical characteristics

Tumour Biol. 2016 Apr;37(4):4841-7. doi: 10.1007/s13277-015-4289-y. Epub 2015 Nov 2.

Abstract

Cytogenetically normal acute myeloid leukemia (CN-AML) constitutes the largest subgroup of AML patients that is associated with molecular alteration. MiRNAs have been shown to be aberrantly expressed in CN-AML. In addition, specific miRNA (miR) expression patterns were found to be associated with certain genetic alterations in these patients. This study investigated the expression level of miR-1, miR-486, and let-7a in 45 CN-AML patients well characterized for FLT3 and/or NPM1 mutations using real-time quantitative RT-PCR and evaluated the association between candidate miRs expression and clinical features. Our data revealed that miR-1 was significantly overexpressed in CN-AML patients, and increasing expression of miR-1 correlated with NPM1 mutation (P < 0.05) and lower hemoglobin level was also observed in patients with miR-1 overexpression (P < 0.05). The expression of miR-1 was much higher in AML-M2 compared with other subtypes. Further, we found significantly increasing miR-486 expression in 40 of 45 (89 %) CN-AML patients. There was no significant association of upregulation of miR-486 with clinical parameters. The expression level of miR-486 was increased in AML-M2 subtype. The levels of let-7a were significantly increased in CN-AML patients compared to the healthy control and significantly higher in the NPM1 ± CN-AML patients. There was no correlation detected between the level of let-7a and FLT3+. An increasing expression level of let-7a was demonstrated in M2 subtype. In addition, our data showed no significant association between increasing let-7a and clinical characteristic. Comparison of peripheral blood and bone marrow results in 30 CN-AML patients showed that there is a considerable concordance between PB and BM in the results of candidate miR levels (P < 0.001). In conclusion, further studies should also be performed to detect functional mechanism of these miRs.

Keywords: Cytogenetically normal AML; let-7a; miR-1; miR-486.

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / pathology
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics*
  • Prognosis
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • MIRN1 microRNA, human
  • MIRN486 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • mirnlet7 microRNA, human
  • nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3