The molecular genetic makeup of acute lymphoblastic leukemia.

Hematology Am Soc Hematol Educ Program. p:389-396, 2012, 10.1182/asheducation.V2012.1.389.3798360

Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy.

In order to access Controlled TARGET ALL 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 Files

• GDC Manifests
  • Controlled-Access Data Download Manifest (6 Files)
  • Open-Access Data Download Manifest (22 Files)
  • WGS CGI Files Download Manifest (305 Files)

• Copy Number
  • TARGET ALL P2 Copy Number Array Level 1 Data (Controlled)
  • TARGET ALL P2 Copy Number Array Level 2 Data (Controlled)
  • TARGET ALL P2 Copy Number Array Level 3 Data
  • TARGET ALL P2 Copy Number Array Metadata
• Gene Expression Array
  • TARGET ALL P2 Gene Expression Array Level 1 Data
  • TARGET ALL P2 Gene Expression Array Level 2 Data
  • TARGET ALL P2 Gene Expression Array Level 3 Data
  • TARGET ALL P2 Gene Expression Array Metadata
• Methylation Array
  • TARGET ALL P2 Methylation Array Level 1 Data
  • TARGET ALL P2 Methylation Array Level 1 Data (Controlled)
  • TARGET ALL P2 Methylation Array Level 2 Data
  • TARGET ALL P2 Methylation Array Level 3 Data
  • TARGET ALL P2 Methylation Array Design Information
  • TARGET ALL P2 Methylation Array Metadata
• mRNA-Seq
  • TARGET ALL P2 mRNA-Seq Level 3 Data
  • TARGET ALL P2 mRNA-Seq Level 3 Data (Controlled)
  • TARGET ALL P2 mRNA-Seq Metadata
• miRNA-Seq
  • TARGET ALL P2 miRNA-Seq Level 3 Data
  • TARGET ALL P2 miRNA-Seq Metadata
• WGS
  • TARGET ALL P1 and P2 WGS L3 Data
  • TARGET ALL P1 and P2 WGS L3 Data (Controlled)
  • TARGET ALL P1 and P2 WGS L4 Data
  • TARGET ALL P2 and P2 WGS Metadata
• WXS
  • TARGET ALL P2 WXS Level 3 Data
  • TARGET ALL P2 WXS Level 3 Data (Controlled)
  • TARGET ALL P2 WXS Design Information
  • TARGET ALL P2 WXS Metadata
• Miscellaneous Files
  • TARGET ALL P2 Sample Matrix

Additional Resources

• TARGET-ALL-P2 at SRA (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.