The incidence of clonal T-cell receptor rearrangements in B-cell precursoracute lymphoblastic leukemia varies with age and genotype

B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) are increasingly treated on risk-adapted protocols based on presenting clinical and biologic al features. Residual molecular positivity of clonal immunoglobulin (IG) an d T-cell receptor (TCR) rearrangements allows detection of patients at an i ncreased risk of relapse. If these rearrangements are to be used for univer sal follow-up, it is important to determine the extent to which they are in formative in different BCP-ALL subsets. We show that IGH V-D-J rearrangemen ts occur in 89% of 163 BCP-ALL, with no significant variation according to age or genotype (BCR-ABL, TEL-AML1, MLL-AF4, and E2A-PBX1). In contrast, TC RG rearrangements, which occur in 60% of patients overall, are frequent in BCR-ABL and TEL-AML1, are less so in MLL-AF4, and are virtually absent in i nfants aged predominantly from 1 to 2 years and in E2A-PBX1 ALLs, Incidence of the predominant TCRD V delta 2-D delta 3 rearrangement decreases with a ge but is independent of genotype. These differences are not due to differe ntial recombination activating gene activity, nor can they be explained ade quately by stage of maturation arrest. Analysis of MLL-AF4 BCP-ALL is in ke eping with transformation of a precursor at an early stage of ontogenic dev elopment, despite the adult onset of the cases analyzed. We postulate that the complete absence of TCRG rearrangement in E2A-PBX1 cases may result fro m deregulated E2A function. These data also have practical consequences for the use of TCR clonality for the molecular follow-up of BCP-ALL. (Blood, 2 000;96:2254-2261) (C) 2000 by The American Society of Hematology.