PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease

Leuk Res. 2002 Apr;26(4):335-43. doi: 10.1016/s0145-2126(01)00130-8.

Abstract

Detection of MRD remains one of the major goals in the treatment of acute lymphoblastic leukemia (ALL). We have used the polymerase chain reaction (PCR)-heteroduplex (HD) analysis to assess and confirm the clonal expansion of T cell receptor (TCR) gamma and delta gene rearrangements in 24 T-ALL patients at diagnosis. 52.4% revealed Vdelta1-Jdelta1; 48% Vdelta2-Ddelta3; 62.5% Vgamma1-Jgamma1 and 46% both Vdelta1-Jdelta1 and Vgamma1-Jgamma1 clonal rearrangements. 6/24 patients had TAL-1 deletion. These clonal markers were used to monitor MRD in remission/relapse bone marrow samples for periods ranging from 6 to 75 months after diagnosis. Patients who relapsed and died revealed a continuous PCR-HD positivity in their clinical remission bone marrow samples. HD analysis established identical diagnostic clone at relapse. Patients who are in long-term clinical and morphological remission achieved PCR-HD negativity in their 8-12 months bone marrow remission samples and continue to be PCR-HD negative. MRD monitored in six patients with two diagnostic PCR--HD positive clonal markers reveal an identical pattern ensuring circumvention of false positive and negative results. Thus, we conclude that PCR followed by HD analysis is a useful technique to monitor MRD in remission/relapse samples in ALL patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Basic Helix-Loop-Helix Transcription Factors
  • Child
  • Child, Preschool
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Deletion
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / genetics*
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / genetics*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / diagnosis
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Male
  • Neoplasm, Residual
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Proto-Oncogene Proteins*
  • Recurrence
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • TAL1 protein, human