Objective: To explore the junctional sequence difference of T cell receptor delta and gamma gene rearrangement in childhood acute lymphoblastic leukemia (ALL) at diagnosis, complete remission (CR) and relapse.
Methods: By using the T-vector molecular cloning and sequencing and polymerase chain reaction, the junctional sequences of TCRdeltaV-D and TCRgammaV-J were dynamically analyzed in 34 bone marrow samples of ALL.
Results: The junctional sequence of TCR delta, gamma gene showed significant difference and regularity before and after remission and during relapsed periods. The sequence of TCRdeltaV-D were analyzed in 24 samples from ALL. Among them, the intact Vdelta2 and 5'Ddelta3 sequences were observed in 10 samples at diagnosis, of which 7 samples had T-->C mutation in Ddelta3 nonamer sequence. The deletions of rearranged Vdelta2, 5'Ddelta3 and Ddelta3 haptamer sequences were found in 11 complete remission (CR) samples with ALL, but none had T-->C mutation in Ddelta3 nonamer sequence. The deletion rate of Vdelta2 or Ddelta3 sequences and the T-->C mutation in Ddelta3 nonamer sequence were extremely differed between samples at diagnosis and in remission (calculate exact probabilities P = 0.001). The junctional rearrangement sequence of 5'Ddelta3 sequences tended to remain intact in 3 relapsed samples. The findings of TCRgammaV-J sequences were similar to that of TCRdeltaV-D in 10 ALL patients.
Conclusion: The difference of TCRdeltaV-D and TCRgammaV-J junctional sequences were related to the development, therapeutic effectiveness and outcome in ALL.