HIGH PREVALENCE OF T-CELL RECEPTOR D-DELTA-2(D-DELTA)J-DELTA REARRANGEMENT IN CD7-POSITIVE EARLY T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA

We have studied the molecular characterization of the T cell receptor (TcR) genes in 16 patients with CD7(+) early T cell acute lymphoblasti c leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rea rrangement was demonstrated in one patient for immunoglobulin heavy ch ain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. F ifteen patients (94%) had rearranged band(s) involving the joining reg ion of the TcR-delta chain gene. In nine cases these were the only rea rrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearr angements were found as well. The D delta 2(D delta)J delta 1 rearrang ement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized i n two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positi ve for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that D DJ delta joining occurs at an early stage during T cell differentiatio n, followed by rearrangements of V delta to the DDJ delta complex. Fur thermore, our findings suggest that DDJ delta recombination occurs ear lier than expression of CyCD3 epsilon protein products. DDJ delta rear rangements have never been observed in non-T cell malignancies, such a s precursor-B-ALL or acute myeloid leukemia. Therefore, detection of D DJ delta rearrangement in the TcR-delta locus is a useful tool to esta blish lineage and clonality of leukemic cells In the most immature sta ges of T cell development.