Integrated stem cell signature and cytomolecular risk determination in pediatric acute myeloid leukemia

Nature Communications. Volume 13, Issue 1: p. 5487, 19 September 2022

10.1038/s41467-022-33244-6

Relapsed or refractory pediatric acute myeloid leukemia (AML) is associated with poor outcomes and relapse risk prediction approaches have not changed significantly in decades. To build a robust transcriptional risk prediction model for pediatric AML, we perform RNA-sequencing on 1503 primary diagnostic samples. While a 17 gene leukemia stem cell signature (LSC17) is predictive in our aggregated pediatric study population, LSC17 is no longer predictive within established cytogenetic and molecular (cytomolecular) risk groups. Therefore, we identify distinct LSC signatures on the basis of AML cytomolecular subtypes (LSC47) that were more predictive than LSC17. Based on these findings, we build a robust relapse prediction model within a training cohort and then validate it within independent cohorts. Here, we show that LSC47 increases the predictive power of conventional risk stratification and that applying biomarkers in a manner that is informed by cytomolecular profiling outperforms a uniform biomarker approach.

In order to access Controlled TARGET AML data using the links below, users must submit an application for Authorized Access via dbGaP as described on dbGaP’s TARGET Study Page. To begin the application process, please view the information and instructions provided on the dbGaP Authorized Access Login Page under “dbGaP Data Download”.

Supplemental Data

• GDC Manifests
  • Controlled-Access Data Download Manifest (8 Files)
  • Open-Access Data Download Manifest (25 Files)
  • WGS CGI Files Download Manifest (209 Files)
• Copy Number Array
  • TARGET AML Copy Number Array Level 1 Data (Controlled)
  • TARGET AML Copy Number Array Level 2 Data (Controlled)
  • TARGET AML Copy Number Array Level 3 Data
  • TARGET AML Copy Number Array Data Metadata
• Gene Expression Array
  • TARGET AML Gene Expression Array Level 1 Data
  • TARGET AML Gene Expression Array Level 2 Data
  • TARGET AML Gene Expression Array Level 3 Data
  • TARGET AML Gene Expression Array Metadata
• mRNA-Seq
  • TARGET AML RNA-Seq Level 3 Data
  • TARGET AML RNA-Seq Level 3 Data (Controlled)
  • TARGET AML RNA-Seq Metadata
• miRNA-Seq
  • TARGET AML miRNA-Seq Level 3 Data
  • TARGET AML miRNA-Seq Level 4 Data
  • TARGET AML miRNA-Seq Metadata
• WXS
  • TARGET AML WXS Level 3 Data
  • TARGET AML WXS Level 3 Data (Controlled)
  • TARGET AML WXS Design
  • TARGET AML WXS Metadata
• Methylation Array
  • TARGET AML Methylation Array Level 1 Data (Controlled)
  • TARGET AML Methylation Array Level 2 Data
  • TARGET AML Methylation Array Level 3 Data
  • TARGET AML Methylation Array Level 4 Data
  • TARGET AML Methylation Array Metadata
• WGS
  • TARGET AML WGS Level 3 Data
  • TARGET AML WGS Level 3 Data (Controlled)
  • TARGET AML WGS Level 4 Data
  • TARGET AML WGS Metadata
• Targeted Capture Sequencing
  • TARGET AML Targeted Capture Sequencing Level 3 Data (Controlled)
  • TARGET AML Targeted Capture Sequencing Design
  • TARGET AML Targeted Capture Sequencing Metadata
• Miscellaneous Files
  • TARGET AML Sample Matrices
  • TARGET AML CGI Requested Reports (Controlled)

Additional Resources

• SRA - SRP012000 (link is external) NCBI

Instructions for Data Download

Open Access Data

1. Download the appropriate manifest file from the publication page
2. Use the manifest file to download data using the GDC Data Transfer Tool (DTT) or the GDC API
   • GDC DTT (Download, User's Guide)
   • GDC API (User’s Guide)

Controlled Access Data

1. Download the appropriate manifest file from the publication page
2. Download a token from the GDC Data Portal
   • GDC Data Portal (Launch, User’s Guide)
3. Use the manifest file and token to download data using the GDC DTT or the GDC API
   • GDC DTT (Download, User’s Guide)
   • GDC API (User’s Guide)

For assistance, please contact the GDC Help Desk: support@nci-gdc.datacommons.io.