Clonal variation of the immunogenotype in relapsed ETV6/RUNX1-positive acute lymphoblastic leukemia indicates subclone formation during early stages of leukemia development

Genes Chromosomes Cancer. 2004 Feb;39(2):156-60. doi: 10.1002/gcc.10305.

Abstract

Recent data suggest that late relapses evolve from an ancestral ETV6/RUNX1-positive (also designated TEL/AML1-positive) clone resulting from secondary changes (ETV6 deletion) that differ from those of the initial leukemia and, as a consequence, may also deviate in their clonotypic immunoglobulin/T-cell receptor (IG/TCR) gene rearrangements. The aim of our study was to compare the immunogenotype and fluorescence in situ hybridization (FISH) patterns of the unrearranged ETV6 allele of matched diagnosis/relapse samples from 12 children with an early or late relapse. We identified varying degrees of differences in the IG/TCR in six of them. A clonal change or evolution of the unrearranged ETV6 allele was also observed in six children but remained unchanged in three. However, these two parameters were not in concordance, nor did the immunogenotype pattern correlate with the duration of the first remission. We therefore propose that the potential of the immunogenotype to diversify depends primarily on the stage of IG/TCR gene configuration of the cell in which the ETV6/RUNX1 gene fusion takes place.

Publication types

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

MeSH terms

  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit
  • Gene Rearrangement / genetics
  • Genes, Immunoglobulin / genetics*
  • Genetic Variation / genetics*
  • Genotype
  • Humans
  • Infant
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Translocation, Genetic / genetics

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • Receptors, Antigen, T-Cell, gamma-delta
  • TEL-AML1 fusion protein