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Deregulation of Mir-1, Mir486, and Let-7A in Cytogenetically Normal Acute Myeloid Leukemia: Association With Npm1 and Flt3 Mutation and Clinical Characteristics Publisher Pubmed



Seyyedi SS1 ; Soleimani M2 ; Yaghmaie M3 ; Ajami M2 ; Ajami M2 ; Pourbeyranvand S4 ; Alimoghaddam K3 ; Akrami SM5
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Authors Affiliations
  1. 1. Department of Medical Genetics, Tehran University of Medical Sciences, International Campus (TUMS—IC), Tehran, Iran
  2. 2. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  3. 3. Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran

Source: Tumor Biology Published:2016


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. © 2015, International Society of Oncology and BioMarkers (ISOBM).
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