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Recent genomic studies have provided a refined genetic map of acute lymphoblastic leukemia (ALL) and increased the number of potential prognostic markers. Therefore, we integrated copy-number alteration data from the 8 most commonly deleted genes, subordinately, with established chromosomal abnormalities to derive a 2-tier genetic classification. The classification was developed using 809 ALL97/99 patients and validated using 742 United Kingdom (UK)ALL2003 patients. Good-risk (GR) genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy-number status for all 8 genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk (PR). Three-quarters of UKALL2003 patients had a GR genetic profile and a significantly improved event-free survival (EFS) (94%) compared with patients with a PR genetic profile (79%). This difference was driven by a lower relapse rate (4% vs 17%), was seen across all patient subgroups, and was independent of other risk factors. Even genetic GR patients with minimal residual disease (>0.01%) at day 29 had an EFS in excess of 90%. In conclusion, the integration of genomic and cytogenetic data defines 2 subgroups with distinct responses to treatment and identifies a large subset of children suitable for treatment deintensification.

Original publication




Journal article



Publication Date





1434 - 1444


Adolescent, Child, Child, Preschool, Cohort Studies, Core Binding Factor Alpha 2 Subunit, Cytogenetic Analysis, Female, Gene Deletion, Gene Dosage, Genes, p16, Genomics, Humans, Infant, Kaplan-Meier Estimate, Male, Neoplasm Proteins, Oncogene Proteins, Fusion, PAX5 Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Proto-Oncogene Proteins c-ets, Repressor Proteins, Risk Factors