Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia

tMultiple lesions in genes that are involved in cell cycle control, proliferation, survival and differentiationunderlie T-cell acute lymphoblastic leukaemia (T-ALL). We translated these biological insights into clinicalpractice to improve diagnostic work-ups and patient management. Combined interphase fluorescencein situ hybridization (CI-FISH), single nucleotide polymorphism (SNP), and gene expression profiles (GEP)were applied in 51 children with T-ALL who were stratified according to minimal residual disease (MRD)risk categories (AIEOP-BFM ALL2000).CI-FISH identified type A abnormalities in 90% of patients. Distribution of each was in line with theestimated incidence in childhood T-ALL: 37.5% TAL/LMO, 22.5% HOXA, 20% TLX3, 7.5% TLX1, and 2.5%NKX2-1. GEP predictions concurred. SNP detected type B abnormalities in all cases, thus linking type Aand B lesions.This approach provided an accurate, comprehensive genomic diagnosis and a complementary GEP-based classification of T-ALL in children. Dissecting primary and secondary lesions within MRD categoriescould improve prognostic criteria for the majority of patients and be a step towards personalized diag-nosis.