Analysis of molecular events in leukemic cells arrested at an early stage of T-cell differentiation

Abstract

We analyzed the rearrangement and expression of T-cell receptor (TCR) genes, including the recently identified TCRδ gene, in 21 patients with T-lineage leukemia/lymphoma. Among 8 patients with CD3-, CD4-, and CD8- (group I), 2 patients showed germline configuration of the TCRδ, γ, β, and α genes and 1 patient demonstrated only TCRδ gene rearrangement. All nine patients with CD3-, CD4+, and/or CD8+ (group II) showed concomitant rearrangements of the TCRδ, γ, and β genes. TCRα gene rearrangement was also observed in two patients. Three of four patients with CD3+ (group III) showed rearrangement of the TCRα gene with deletion of both alleles or of a single allele of the TCRδ gene. With Northern blot analysis, full-length transcripts of the TCRδ gene were detected in 3 of 15 examined patients. All were restricted to group I or group II. In contrast, full-length transcripts of TCRβ and α were observed mainly in samples from groups II and III. Based on these findings, rearrangement of the TCRδ gene may be the earliest event in T-cell differentiation, preceding rearrangement of the other TCR genes.