TCR-beta chain gene rearrangement and expression in human T-cell development and in leukemia

T-cell receptor TCR-beta gene expression is an early event during human ontogenesis since the majority of thymocytes express cytoplasmic beta chain as early as the 15th week of gestation, when a complete VDJ rearrangement and functional 1.3-kb beta gene transcript are detectable. We report here our contribution with those of others on the analysis of TCR-beta gene ontogenesis. By sequencing beta gene transcripts we have demonstrated that beta gene N-regions increase dramatically in the thymus after the 20th week and that the period between 20-30 weeks is of critical importance for the acquisition of N-diversity. A correlation between TdT and N-region expression also exists. An ordered expression of TdT and cytoplasmic beta chain occurs in humans starting around the 20th week, similar to the sequence of coordinated expression of TdT and cytoplasmic mu chains detectable in B-cell precursors. TCR-beta gene behavior in T-cell neoplasms, in 'biphenotypic' leukemias and in B-ALL is also discussed. An interesting study of seven cases of B-ALL with complete V(D)J beta gene rearrangement is analyzed, as is its implication for further analysis in B-cell leukemia.