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Does activation of the TAL1 gene occur in a majority of patients with T-
cell acute lymphoblastic leukemia? A pediatric oncology group study
RO Bash, S Hall, CF Timmons, WM Crist, M Amylon, RG Smith and R Baer
Department of Pediatrics, University of Texas Southwestern Medical Center,
Dallas 75235-9048, USA.
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).
Volume 86,
Issue 2,
pp. 666-676,
07/15/1995
Copyright © 1995 by The American Society of Hematology
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