TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse

Leukemia. 2004 Dec;18(12):1971-80. doi: 10.1038/sj.leu.2403505.

Abstract

Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene rearrangements were detected in 35% of childhood (n=161) and adult (n=172) precursor-B-ALL patients (Vbeta-(Dbeta)-Jbeta in 25%; Dbeta-Jbeta in 15%). The presence of TCRB rearrangements showed a significant relation with age (highest frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1 transcripts, and was associated with relatively high frequencies of IGK-Kde, TCRG, and Vdelta2-Jalpha rearrangements. In 62 out of 65 patients with Southern blot-detected Vbeta-(Dbeta)-Jbeta and/or Dbeta-Jbeta rearrangements, at least one TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20 out of 24 (83%) Vbeta-(Dbeta)-Jbeta rearrangements and eight out of 14 (57%) Dbeta-Jbeta rearrangements remained stable. Using real-time quantitative PCR, a quantitative range < or =10(-4) was obtained in 64% of TCRB gene rearrangements and in 86% of cases a sensitivity < or =10(-4) was obtained. In conclusion, TCRB gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively stable and sensitive PCR targets for detection of minimal residual disease, particularly if this concerns complete Vbeta-(Dbeta)-Jbeta rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Southern
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Genes, T-Cell Receptor beta / genetics*
  • Humans
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / genetics
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein