Document Detail


A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia.
MedLine Citation:
PMID:  23765227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a 'core enriched' (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CE(high)) associated with FLT3-internal tandem duplication, WT1 and RUNX1 mutations, wild-type CEBPA and TET2, and high ERG, BAALC and miR-155 expression. CE(high) patients had a lower complete remission (CR) rate (P=0.003) and shorter disease-free (DFS, P<0.001) and overall survival (OS, P<0.001) than CE(low) patients. These associations persisted in multivariable analyses adjusting for other prognosticators (CR, P=0.02; DFS, P<0.001; and OS, P<0.001). CE(high) status was accompanied by a characteristic miR expression signature. Fifteen miRs were upregulated in both younger and older CE(high) patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML.
Authors:
K H Metzeler; K Maharry; J Kohlschmidt; S Volinia; K Mrózek; H Becker; D Nicolet; S P Whitman; J H Mendler; S Schwind; A-K Eisfeld; Y-Z Wu; B L Powell; T H Carter; M Wetzler; J E Kolitz; M R Baer; A J Carroll; R M Stone; M A Caligiuri; G Marcucci; C D Bloomfield
Related Documents :
8885057 - Growth factors and cytokines in uterine leiomyomas.
18505847 - Corticosteroid receptors involved in stress regulation in common carp, cyprinus carpio.
15072547 - Estrogen regulation in human breast cancer cells of new downstream gene targets involve...
19013437 - Novel progesterone receptor modulators with gene selective and context-dependent partia...
12914657 - Duplication is more common among laterally transferred genes than among indigenous genes.
11306097 - Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by ubiquitou...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-14
Journal Detail:
Title:  Leukemia     Volume:  27     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-09     Completed Date:  2013-12-10     Revised Date:  2014-01-15    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  2023-31     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Cytogenetic Analysis
Female
Humans
Leukemia, Myeloid, Acute / genetics*,  mortality,  therapy
Male
MicroRNAs / genetics*
Middle Aged
Oligonucleotide Array Sequence Analysis
Prognosis
Remission Induction
Stem Cells / metabolism*,  pathology
Survival Rate
Transcriptome*
Tumor Markers, Biological / genetics*
Young Adult
Grant Support
ID/Acronym/Agency:
CA101140/CA/NCI NIH HHS; CA114725/CA/NCI NIH HHS; CA129657/CA/NCI NIH HHS; CA140158/CA/NCI NIH HHS; CA16058/CA/NCI NIH HHS; CA31946/CA/NCI NIH HHS; CA33601/CA/NCI NIH HHS; CA77658/CA/NCI NIH HHS; P50 CA140158/CA/NCI NIH HHS; U10 CA026806/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/Tumor Markers, Biological

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


Previous Document:  Flow cytometric detection of dyserythropoiesis: a sensitive and powerful diagnostic tool for myelody...
Next Document:  Toll-like receptor alterations in myelodysplastic syndrome.