Rearrangement of the T-cell receptor delta genes in human T-cell leukemias
L Foroni, M Laffan, T Boehm, TH Rabbitts, D Catovsky and L Luzzatto
Department of Haematology, Royal Post Graduate Medical School, London, UK.
Two distinct types of T-cell receptors (TCR), designated alpha beta and
gamma delta, have been identified on the surface of T cells. In the adult,
T cells bearing the gamma delta TCR are a minority and they have the
phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements
of the TCR alpha, beta, and gamma genes have been extensively investigated
in a variety of lymphoproliferative disorders. Because the TCR delta gene
has been cloned only recently, no comparable information exists with
respect to this in human leukemias. We report the analysis of the TCR delta
gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell
leukemias, 4 acute myeloid leukemias of difficult classification, and 12
normal controls. The TCR delta genes were structurally modified in all
T-cell disorders and in germ-line configuration in all controls and all but
one case of non-T-cell leukemias tested. In one case of T-chronic
lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and
expression of TCR gamma and delta (but not alpha and beta), suggesting that
leukemic transformation took place in a cell bearing a TCR gamma delta
rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic
leukemia, only delta was rearranged out of the three TCR genes tested. This
finding is in keeping with the suggestion that the TCR delta gene might be
the first to rearrange in T cell ontogeny, and that its mode of
rearrangement may play a role in the subsequent choice of the cell between
production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene
analysis can provide novel information of the clonal nature of T-cell
disorders, particularly if the analysis of the beta and gamma genes has not
been helpful.
Volume 73,
Issue 2,
pp. 559-565,
02/01/1989
Copyright © 1989 by The American Society of Hematology