Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study.

  • Bash R
  • Hall S
  • Timmons C
 et al. 
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Abstract

Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles).

Author-supplied keywords

  • Alleles
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Marrow
  • Burkitt Lymphoma
  • Child
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Gene Expression Regulation, Leukemic
  • Gene Rearrangement
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Neoplastic Stem Cells
  • Pleural Effusion
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins
  • T-Lymphocytes
  • Transcription Factors
  • biosynthesis
  • genetics
  • metabolism
  • pathology

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Authors

  • R O Bash

  • S Hall

  • C F Timmons

  • W M Crist

  • M Amylon

  • R G Smith

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