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PMID: 18187662 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia.

Blood ·Vol. 111 ·No. 6 ·2008-03-15 ·Pages 3183-9

Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, Fabbri M, Coombes K, Alder H, Nakamura T, Flomenberg N, Marcucci G, Calin GA, Kornblau SM, Kantarjian H, Bloomfield CD, Andreeff M, Croce CM

Abstract

MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34(+) cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34(+) normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Antigens, CD34/metabolism Blood Cell Count Cell Lineage Chromosomes, Human, Pair 11/genetics Chromosomes, Human, Pair 8/genetics Cytogenetics Down-Regulation Female Gene Expression Regulation, Neoplastic Humans Karyotyping Leukemia, Erythroblastic, Acute/diagnosis,genetics,pathology,therapy Male MicroRNAs/genetics Middle Aged Mutation/genetics Prognosis Stem Cells/cytology,metabolism Treatment Outcome Trisomy/genetics
Chemicals
Antigens, CD34 MicroRNAs
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Garzon Ramiro
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Volinia Stefano
Liu Chang-Gong
Fernandez-Cymering Cecilia
Palumbo Tiziana
Pichiorri Flavia
Fabbri Muller
Coombes Kevin
Alder Hansjuerg
Nakamura Tatsuya
Flomenberg Neal
Marcucci Guido
Calin George A
Kornblau Steven M
Kantarjian Hagop
Bloomfield Clara D
Andreeff Michael
Croce Carlo M
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2007-07-098749
Published
2008-03-15
Epub
2008-00-10
Pages
3183-9
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2265455
Subset
IM
Grants
NCI NIH HHS · CA16058 · United States
NCI NIH HHS · P01CA76259 · United States
NCI NIH HHS · P01 CA081534 · United States
NCI NIH HHS · P01 CA076259 · United States
NCI NIH HHS · P01CA81534 · United States
NCI NIH HHS · P30 CA016058 · United States
NCI NIH HHS · P01 CA055164 · United States
External Links
PubMed source DOI: 10.1182/blood-2007-07-098749 PMC Full Text View journal details
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