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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 04, 2012 |
| Title |
Identification of prognostic gene signatures in AML |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
In addition, this data set has also been used to identify a common prognostic gene signature in human AML (Li Z. et al., unpublished).
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| Overall design |
93 human AML samples bearing various cytogenetic and molecular abnormalities are used to identify miR-181 target genes and a common prognostic gene signature.
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| Contributor(s) |
Li Z, Huang H, Chen P, He C, Jiang X, Li Y, Radmacher MD, Maharry K, Elkahloun A, Yang X, Arnovitz S, Delwel R, Dohner K, Zhang Z, Shen C, Neilly MB, Zhang Y, Larson RA, Le Beau MM, Caligiuri MA, Bullinger L, Valk PJ, Lowenberg B, Liu PP, Marcucci G, Rowley JD, Bloomfield CD, Chen J |
| Citation(s) |
22251480, 23079661, 28500307 |
| Submission date |
Jun 28, 2011 |
| Last update date |
Feb 18, 2019 |
| Contact name |
chunjiang he |
| Organization name |
university of chicago
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| Street address |
900 east 57th st
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| City |
chicago |
| State/province |
il |
| ZIP/Postal code |
60637 |
| Country |
USA |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (93)
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| This SubSeries is part of SuperSeries: |
| GSE30257 |
Identification of a common prognostic gene signature and its association with miR-181 regulation in human acute myeloid leukemia |
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| Relations |
| BioProject |
PRJNA154793 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30285_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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