Immunophenotypic and immunogenotypic characteristics of TCR gamma delta(+)T cell acute lymphoblastic leukemia

Thirty T cell receptor (TCR)gamma delta(+) T cell acute lymphoblastic leuke mias (T-ALL) were analyzed for their immunophenotype, as well as for the re arrangements and junctional regions of the TCRG and TCRD genes. In 15 cases membrane expression of TCR gamma delta proteins could be studied extensive ly by flow cytometry with a new V gamma/V delta antibody panel. Virtually a ll TCR gamma delta(+) T-ALLs expressed TdT, CD2, CD3, CD5, CD6, and CD7, bu t they were heterogeneous in their CD1/CD4/CD8 immunophenotype. The majorit y expressed either CD4(+)/CD8(-) or CD4(+)/CD8(+), whereas only 7/30 TCR ga mma delta(+) T-ALLs lacked both antigens. Despite heterogeneity in the rear ranged TCRG and TCRD genes, we found preferential protein expression of V g amma 1 (21/30), J gamma 2.3 (19/30) and C gamma 2 (21/30) gene products in the TCR gamma delta(+) T-ALL. Expressed TCRD genes were largely limited to V delta 1-J delta 1, except for six patients who expressed non-V delta 1 TC RG chains (V delta 2-J delta 1, V delta 2-J5 delta 3, V delta 3-J delta 1, V delta 6-J delta 2, and two V alpha-J delta 1). In spite of the relatively limited combinatorial repertoire of the TCRG and TCRD genes, the junctiona l region diversity of the expressed genes was extensive. The V gamma/V delt a antibody panel confirmed the predominant, but not exclusive, expression o f V gamma 1 and V delta 1 proteins. Importantly, not a single T-ALL express ed the common peripheral blood V gamma 9(+)/V delta 2(+) phenotype. These i mmunogenotypic and immunophenotypic characteristics represent excellent tar gets for flow cytometric and PCR-based detection of 'minimal residual disea se' in all TCR gamma delta(+) T-ALL. Comparison of non-V delta 1(+) TCR gam ma delta T-ALLs with the more common V delta 1(+) type showed a trend towar ds a more mature immunogenotype in the former. Firstly, more complete TCRD rearrangements were identified on the non-expressed allele in the non-V del ta 1(+) group (83% vs 43%); secondly, a higher frequency of 'end-stage' J g amma 2.3 gene rearrangements was found in non-V delta 1 cases on both TCRG alleles (83% vs 66%); thirdly, a higher frequency of complete TCRB rearrang ements was found in non-V delta 1 cases (79% vs 50%).