|Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene.|
|PMID: 23022987 Owner: NLM Status: MEDLINE|
|Acute myeloid leukemia (AML) with t(8;16)(p11;p13) (t(8;16) AML) has unique clinico-biological characteristics, but its microRNA pattern is unknown. We analyzed 670 microRNAs in seven patients with t(8;16) AML and 113 with other AML subtypes. Hierarchical cluster analysis showed that all t(8;16) AML patients grouped in an independent cluster. Supervised analysis revealed a distinctive signature of 94-microRNAs, most of which were downregulated, including miR-21 and cluster miR-17-92. The mRNA expression analysis of two known transcription factors of these microRNAs (STAT3 and c-Myc, respectively) showed significant downregulation of STAT3 (P=0.04). A bioinformatic analysis showed that 29 of the downregulated microRNAs might be regulated by methylation; we treated a t(8;16) AML sample with 5-aza-2'-deoxycytidine (5-AZA-dC) and trichostatin A and found that 27 microRNAs were re-expressed after treatment. However, there was no difference in methylation status between t(8;16) and other AML subtypes, either overall or in the microRNA promoter. Cross-correlation of mRNA and microRNA expression identified RET as a potential target of several microRNAs. A Renilla-luciferase assay and flow cytometry after transfection with pre-microRNAs confirmed that RET is regulated by miR-218, miR-128, miR-27b, miR-15a and miR-195. In conclusion, t(8;16) AML harbors a specific microRNA signature that is partially epigenetically regulated and targets RET proto-oncogene.|
|M Díaz-Beyá; A Navarro; G Ferrer; T Díaz; B Gel; M Camós; M Pratcorona; M Torrebadell; M Rozman; D Colomer; M Monzo; J Esteve|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-10-01|
|Title: Leukemia Volume: 27 ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2013 Mar|
|Created Date: 2013-03-06 Completed Date: 2013-04-30 Revised Date: 2013-06-03|
Medline Journal Info:
|Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England|
|Languages: eng Pagination: 595-603 Citation Subset: IM|
|Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.|
|APA/MLA Format Download EndNote Download BibTex|
Aged, 80 and over
Azacitidine / analogs & derivatives
CREB-Binding Protein / genetics*
Chromosomes, Human, Pair 16 / genetics*
Chromosomes, Human, Pair 8 / genetics*
DNA, Neoplasm / genetics
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Histone Acetyltransferases / genetics*
Leukemia, Myeloid, Acute / genetics*, pathology
MicroRNAs / genetics*
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Fusion / genetics
Polymerase Chain Reaction
Proto-Oncogene Proteins c-ret / genetics*
Translocation, Genetic / genetics*
Tumor Cells, Cultured
Tumor Markers, Biological / genetics
|0/CREBBP protein, human; 0/DNA, Neoplasm; 0/MicroRNAs; 0/Oncogene Proteins, Fusion; 0/Tumor Markers, Biological; 320-67-2/Azacitidine; 776B62CQ27/decitabine; EC 22.214.171.124/CREB-Binding Protein; EC 126.96.36.199/Histone Acetyltransferases; EC 188.8.131.52/KAT6A protein, human; EC 184.108.40.206/Proto-Oncogene Proteins c-ret; EC 220.127.116.11/RET protein, human|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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