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Study Description

Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia characterized by multiple whole chromosomal losses and very poor outcome. Here we report an integrative genomic analysis that identifies multiple subtypes of hypodiploid ALL characterized by variation in the degree of aneuploidy, distinct submicroscopic deletions and sequence mutations and gene expression profile. Near haploid ALL cases (24-31 chromosomes) have a high frequency of alterations of genes regulating Ras pathway and cytokine receptor signaling (66.2%; NF1, NRAS, KRAS, PTPN11, FLT3, and PAG1), IKZF3 (encoding the lymphoid transcription factor AIOLOS), and a histone gene cluster at 6p22. Low hypodiploid cases (32-39 chromosomes) are enriched for IKZF2 (HELIOS) and RB1 alterations, but have a low frequency of Ras/signaling alterations. A striking finding was exclusivity of Ras/signaling and IKZF2/3 alterations, and biochemical evidence of Ras pathway activation in both near haploid and low hypodiploid ALL. Together, these findings provide critical new insights into the genetic basis of hypodiploid ALL, and indicate that therapeutic targeting of the Ras pathway should be pursued in this disease.

  • Study Types: Case Set, Tumor vs. Matched-Normal, Xenograft
  • Number of study subjects that have individual level data available through Authorized Access: 20

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Primary pediatric hypodiploid acute lymphoblastic leukemia cases with material available for genome-wide profiling.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq 2000 N/A N/A
Study History

SNP 6.0 profiling of DNA copy number alterations was performed on primary human tumors.

Selected publications
Diseases Related to Study (MESH terms)
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Charles Mullighan, MBBS(Hons), MSc, MD. Dept. of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Institute
    • St. Jude Children's Research Hospital, Memphis, TN, USA
  • Funding Source
    • NCI RC4CA156329 "Identifying the spectrum of genetic alterations in high risk acute leukemia". National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    • Partners for Cures: "Genomic analysis of hypodiploid acute lymphoblastic leukemia"
    • St. Baldrick's Foundation Research Grant: "Genomic analysis of hypodiploid acute lymphoblastic leukemia"