title: Deregulation of miR-1, miR486, and let-7a in cytogenetically normal acute myeloid leukemia: association with NPM1 and FLT3 mutation and clinical characteristics.
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.
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, International Campus (TUMS-IC), Tehran, Iran.
authors.forename: Samaneh Sadat
authors.initials: SS
authors.lastname: Seyyedi
authors.affiliation: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Yaghmaie
authors.affiliation: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Monireh
authors.initials: M
authors.lastname: Ajami
authors.affiliation: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Ajami
authors.affiliation: Department of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Pourbeyranvand
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran. akramism@tums.ac.ir.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Akrami
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C544547:MIRN1 microRNA, human; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C487931:mirnlet7 microRNA, human; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Cytogenetically normal AML; let-7a; miR-1; miR-486