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 huma n ontogenesis since the majority of thymocytes express cytoplasmic bet a chain as early as the 15th week of gestation, when a complete VDJ re arrangement 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 h ave 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 correlat ion between TdT and N-region expression also exists. An ordered expres sion of TdT and cytoplasmic beta chain occurs in humans starting aroun d the 20th week, similar to the sequence of coordinated expression of TdT and cytoplasmic mu chains detectable in B-cell precursors. TCR-bet a gene behavior in T-cell neoplasms, in 'biphenotypic' leukemias and i n B-ALL is also discussed. An interesting study of seven cases of B-AL L with complete V(D)J beta gene rearrangement is analyzed, as is its i mplication for further analysis in B-cell leukemia.