α, β and γ T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias

Abstract

We have studied the arrangement of the .alpha., .beta. and .gamma.T cell receptor (TCR) genes in 27 patients with T cell lymphoproliferative disorders. Nine patients had acute lymphoblastic leukaemia (T-ALL), nine patients had prolymphocytic leukaemia (PLL), six patients presented with a T-CLL/T-lymphocytosis syndrome, two patients had Sezary syndrome (SS) and one patient had HTLV-I positive T-cell leukaemia/lymphoma (ATLL). .alpha. TCR gene rearrangement could be demonstrated by the use of three available probes in only one case. By contrast, both .beta. and .gamma. TCR gene rearrangement could be demonstrated by Southern blot analysis of DNA samples digested with appropriate restriction enzymes in the majority of cases. In general, when rearrangements were present they involved both alleles. The proportion of rearranged chromosomes was lower in T-ALL than in other forms of T-cell leukaemia and it was lower in the cases with the CD4-/CD8+ phenotype than in those with CD4+/CD8-phenotype. In three out of 34 cases of B-cell leukaemia the TCR .beta.-gene but not the TCR .gamma.-gene was rearranged, just as in two out of 26 cases of T-cell leukaemia the immunoglobulin (Ig) heavy chain but not the light chain genes were rearranged. These data suggest that development of the machinery required for gene rearrangement may precede commitment to B or T cell lineage. The use of this technique is especially useful for the classification of cases of ALL in which the cells are negative with respect to most current phenotypic markers and in cases of T cell lymphocytosis in which the finding of a gene rearrangement identifies a monoclonal cell population.