Rearrangement and diversification of T-cell receptor delta genes in acute lymphoblastic leukemia

The current study was designed to determine the nucleotide sequence of two distinct T-cell-receptor delta chain (TCR delta) rearrangements which account for 95% of all rearranged alleles in common non-T, non-B lymphoid precursor acute lymphoblastic leukemia (LP-ALL). The results presented demonstrate that TCR delta rearrangements in LP-ALL are incomplete, immature, and involve V delta 2 to D delta 3 or D delta 2 to D delta 3 joints. These rearrangements are found in most cases of ALL. These results are consistent with the hypothesis that these leukemias originate in multipotent lymphoid precursor cells. The remarkable diversity of the rearrangements detected by polymerase chain reaction, cloning and sequencing demonstrates the clonal specificity and potential for detection of leukemic residual disease. However, in some cases the number of nucleotide differences may not be sufficient for the discrimination of leukemic and non-leukemic cells carrying V delta 2-(D)-D delta 3 rearrangements. A novel inversional rearrangement was demonstrated in one leukemia. This novel inversional rearrangement potentially increases the degree of diversity of the junctional region which encodes the antigen binding domain of TCR delta.