Document Detail


Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene.
MedLine Citation:
PMID:  23022987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-01
Journal Detail:
Title:  Leukemia     Volume:  27     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2013 Mar 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  595-603     Citation Subset:  IM    
Affiliation:
Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Azacitidine / analogs & derivatives
CREB-Binding Protein / genetics*
Chromosomes, Human, Pair 16 / genetics*
Chromosomes, Human, Pair 8 / genetics*
Cluster Analysis
DNA Methylation
DNA, Neoplasm / genetics
Female
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Gene Rearrangement
Histone Acetyltransferases / genetics*
Humans
Leukemia, Myeloid, Acute / genetics*,  pathology
Male
MicroRNAs / genetics*
Middle Aged
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Fusion / genetics
Polymerase Chain Reaction
Prognosis
Proto-Oncogene Proteins c-ret / genetics*
Translocation, Genetic / genetics*
Tumor Cells, Cultured
Tumor Markers, Biological / genetics
Young Adult
Chemical
Reg. No./Substance:
0/CREBBP protein, human; 0/DNA, Neoplasm; 0/MicroRNAs; 0/Oncogene Proteins, Fusion; 0/Tumor Markers, Biological; 320-67-2/Azacitidine; 776B62CQ27/decitabine; EC 2.3.1.48/CREB-Binding Protein; EC 2.3.1.48/Histone Acetyltransferases; EC 2.3.1.48/KAT6A protein, human; EC 2.7.10.1/Proto-Oncogene Proteins c-ret; EC 2.7.10.1/RET protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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