Relationship between rearrangement and transcription of the T-cell receptor alpha, beta, and gamma genes in B-precursor acute lymphoblastic leukemia

Abstract

Transcription of the T-cell receptor (TCR)-gamma, beta, and alpha genes has been analyzed in 29 patients with B-precursor acute lymphoblastic leukemia (ALL) by northern blotting analysis. In addition, the configuration of the TCR-alpha gene was examined using newly developed genomic J alpha probes capable of detecting TCR-alpha gene rearrangements involving joining (J)alpha regions up to 85 kilobase (kb) from constant (C)alpha. In this study, TCR-alpha gene rearrangements were detected in 16 of the 29 patients. Thus, the frequency of TCR-alpha gene rearrangements in B precursor ALL was as high as with TCR-gamma (15 of 29) and was higher than observed for TCR-beta (nine of 29). Truncated transcripts were frequently observed in cells with rearrangements of the TCR-beta or alpha gene. In contrast, TCR-gamma transcripts were detected in only one patient despite the high incidence of TCR-gamma gene rearrangements. Results presented here suggest that although expression of TCR genes was weak in B-precursor ALL cells compared with T-lineage cells, these genes experience both transcriptional and recombinational crossover in B-precursor ALL. The results also suggest that neither transcription nor gene rearrangement, when examined alone, are sufficient to assign T or B lymphocyte lineage in lymphoblastic leukemia.