Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases

Eur J Haematol. 2002 Jan;68(1):31-41. doi: 10.1034/j.1600-0609.2002.00547.x.

Abstract

Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aneuploidy
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosome Banding
  • Chromosomes, Human / genetics
  • Chromosomes, Human / ultrastructure*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 1 / ultrastructure
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 21 / ultrastructure
  • Chromosomes, Human, Pair 8 / genetics
  • Chromosomes, Human, Pair 8 / ultrastructure
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins / genetics
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Genes, abl
  • Genes, p16
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Infant
  • Infant, Newborn
  • Interphase
  • Karyotyping / methods*
  • Leukemia, T-Cell / genetics
  • Male
  • Myeloid-Lymphoid Leukemia Protein
  • Oncogene Proteins, Fusion / genetics
  • Philadelphia Chromosome
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / classification
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Proto-Oncogenes*
  • Transcription Factors*
  • Translocation, Genetic / genetics

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • KMT2A protein, human
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Fusion Proteins, bcr-abl