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

Leuk Res. 2013 Aug;37(8):928-35. doi: 10.1016/j.leukres.2013.04.005. Epub 2013 Jun 2.

Abstract

Multiple lesions in genes that are involved in cell cycle control, proliferation, survival and differentiation underlie T-cell acute lymphoblastic leukaemia (T-ALL). We translated these biological insights into clinical practice to improve diagnostic work-ups and patient management. Combined interphase fluorescence in 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 the estimated 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 A and 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 categories could improve prognostic criteria for the majority of patients and be a step towards personalized diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • Genetic Predisposition to Disease / genetics
  • Genomics / methods*
  • Genotype
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Karyotype
  • Male
  • Neoplasm, Residual / genetics*
  • Polymorphism, Single Nucleotide
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Reproducibility of Results
  • Sensitivity and Specificity