THE HUMAN T-CELL V-GAMMA GENE LOCUS - CLONING OF NEW SEGMENTS AND STUDY OF V-GAMMA REARRANGEMENTS IN NEOPLASTIC T AND B-CELLS

  • 1 August 1988
    • journal article
    • research article
    • Vol. 72  (2) , 776-783
Abstract
The authors have analyzed the involvement of V.gamma. and J.gamma. segments in TRG.gamma. rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG.gamma. are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V.gamma.11 and .psi.V.gamma.12, which rearranges in T- and B-neoplastic cells. To date three subgroups of translatable V.gamma. segments have been described. The authors show that V.gamma.11 is the unique member of a new fourth V.gamma. subgroup that also rearranges in normal polyclonal T cells and that .psi.V.gamma.12 is located at 5-kilobase (kb) downstream to V.gamma.11. As shown by DNA sequence analysis, V.gamma.11 shares a 60% homology with V.gamma.10 (third subgroup) and a 50% homology with V.gamma.9 (second subgroup) but no appreciable homology with the V.gamma. segments from the first family. In contrast to .psi.V.gamma.12, V.gamma.11 is translatable. In this paper the authors have also attempted to determine which V.gamma. segments were rearranged in the ALL cases by hybridization with a J.gamma. probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J.gamma.1 or J.gamma.2 involvement, the authors have identifid the corresponding V.gamma. segments and have not found any other rearrangements suggestive of the existence of further V regions. The V.gamma. segments, belonging to the first subgroup, were the most frequently used (41 alleles). V.gamma.9, V.gamma.10, V.gamma.11, and .psi.V.gamma.12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo .psi.V.gamma.1, .psi.V.gamma.5, and .psi.V.gamma.6 segments were found. Pseudo V.gamma. segments were not found rearranged in T cells, while V.gamma.2 and V.gamma.4, segments are frequently used. In contrast to the V.gamma.I gene rearrangements, the involvement of the V.gamma.II, V.gamma.III, and V.gamma.IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+). Analysis of the involvement of joining segments demonstrated that J.gamma.1 and J.gamma.2 were rearranged much more frequently than J.gamma.P, J.gamma.P1, and J.gamma.P2. The analysis of V.gamma., segment deletions was consistent with rearrangements by loop excision showing the localization of the V.gamma.IV subgroup 3'' to the first, second, and third subgroups and 5'' to the joining segments.