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| Status |
Public on Dec 02, 2016 |
| Title |
A 17-Gene Stemness Score for Rapid Identification of High-Risk AML Patients [NanoString] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In AML, most patients are initiated on standard chemotherapy and afterwards assigned to a post-remission strategy based on genetically-defined risk categories. However, outcomes remain heterogeneous, indicating the need for novel biomarker tests that can rapidly and accurately identify high-risk patients, allowing better stratification of both induction and post-remission therapy. As patient outcomes are linked to leukemia stem cell (LSC) properties that confer therapy resistance and drive relapse, LSC-based biomarkers may be highly informative. We tested 227 CD34/CD38 cell fractions from 78 AML patients for LSC activity in xenotransplantation assays. Comparison of microarray-based gene expression (GE) profiles between 138 LSC+ and 89 LSC? fractions identified 104 differentially-expressed LSC-specific genes. To obtain prognostic signatures, we performed statistical regression analysis of LSC GE against patient outcome using a training cohort of 495 AML patients treated with curative intent. A score calculated as the weighted sum of expression of 17 LSC signature genes (LSC17) was strongly associated with survival in 4 independent datasets (716 AML cases) spanning all risk categories in multi-variate analysis; an optimized 3-gene sub-score (LSC3) was prognostic in favorable risk subsets. These scores were robust across GE technology platforms, including the clinically serviceable NanoString system (LSC17: HR=2.73, P<0.0001; LSC3: HR=6.3, P<0.02). The LSC17 and LSC3 scores provide rapid and accurate identification of high-risk patients for whom conventional chemotherapy is non-curative. These scores will enable evaluation in clinical trials of whether such patients may benefit from novel and/or more intensified therapies during induction or in the post-remission setting.
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| Overall design |
307 primary AML patient samples were analyzed for mRNA expression of 17 LSC signature and 9 reference genes. One lane of each NanoString cartridge was reserved for synthetic oligonucleotides to control for batch effects.
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| Contributor(s) |
Ng SW, Mitchell A, Kennedy JA, Chen CW, McLeod JL, Ibrahimova N, Arruda A, Popescu A, Gupta V, Schimmer AD, Schuh AC, Yee KW, Bullinger L, Metzeler KH, Herold T, Buske C, Löwenberg B, Valk PJ, Zandstra PW, Minden MD, Dick JE, Wang JC |
| Citation(s) |
27926740 |
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| Submission date |
Dec 14, 2015 |
| Last update date |
Dec 19, 2016 |
| Contact name |
Stanley Ng |
| E-mail(s) |
stanleywk.ng@mail.utoronto.ca
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| Organization name |
Univerity of Toronto
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| Street address |
160 College Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5S 3E1 |
| Country |
Canada |
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| Platforms (1) |
| GPL21241 |
NanoString Expression Assay, nCounter Prognostic LSC mRNA signature for AML |
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| Samples (307)
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| This SubSeries is part of SuperSeries: |
| GSE76009 |
A 17-Gene Stemness Score for Rapid Identification of High-Risk AML Patients |
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| Relations |
| BioProject |
PRJNA306006 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76004_NanoString_LSC_signature_raw_mRNA.txt.gz |
15.3 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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