Rearrangement and expression of T-cell receptor delta genes in T-cell acute
lymphoblastic leukemias
JJ van Dongen, IL Wolvers-Tettero, F Wassenaar, J Borst and P van den Elsen
Department of Immunology, University Hospital Dijkzigt/Erasmus University,
Rotterdam, The Netherlands.
We have analyzed T-cell receptor delta (TcR-delta) gene rearrangement and
transcription in appropriately phenotyped mononuclear cells derived from 12
patients with T-cell acute lymphoblastic leukemia (T-ALL). The T-ALL cells
were also analyzed for rearrangement and transcription of the T-cell
receptor(TcR)-beta and gamma genes as well as for the presence of TcR-alpha
gene transcripts. Four T-ALLs expressed TcR-gamma delta at the cell
surface, while three expressed TcR-alpha beta. The other five T-ALLs did
not express a TcR-CD3 complex on their cell membrane. The TcR-gamma delta +
T-ALL had rearranged both TcR-delta gene alleles and contained mature 2.2
and 1.5 kb TcR-delta transcripts. In one case, immature 1.9 and 1.2 kb
TcR-delta transcripts were also found. Furthermore they contained mature
TcR-gamma mRNA, mature or immature TcR-beta mRNA, but no TcR-alpha mRNA.
The three TcR-alpha beta + T-ALLs contained mature alpha and beta
transcripts, but lacked TcR- delta transcripts as a result of deletion of
both TcR-delta gene alleles. These data are in line with a mutually
exclusive expression of TcR-alpha and -delta genes, which may be important
to ensure the presence of only one type of TcR per T cell. One of the five
CD3- T- ALLs had germline TcR-beta, gamma, and delta genes. The other four
CD3- T-ALLs had rearranged their TcR-beta, gamma, and delta genes and
contained immature 1.9 and 1.2 kb TcR-delta gene transcripts. Remarkably,
one of these T-ALLs also contained TcR-alpha transcripts in addition to the
immature TcR-delta transcripts, which was in line with the deletion of one
TcR-delta gene allele and rearrangement of the other allele. This suggests
that prevention of dual receptor expression may not only be regulated by
the presence of germline TcR-alpha genes in TcR-gamma delta + cells or by
deletion of both TcR-delta gene alleles in TcR-alpha beta + cells, but also
via other regulation mechanisms. Finally, our data indicated that the
combinatorial repertoire of the TcR-delta genes is limited, which has also
been described for the TcR-gamma genes.
Volume 74,
Issue 1,
pp. 334-342,
07/01/1989
Copyright © 1989 by The American Society of Hematology