TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse

Abstract

Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene rearrangements were detected in 35% of childhood (n=161) and adult (n=172) precursor-B-ALL patients (V–(D)–J in 25%; D–J in 15%). The presence of TCRB rearrangements showed a significant relation with age (highest frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1 transcripts, and was associated with relatively high frequencies of IGK-Kde, TCRG, and V2-J rearrangements. In 62 out of 65 patients with Southern blot-detected V–(D)–J and/or D–J rearrangements, at least one TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20 out of 24 (83%) V–(D)–J rearrangements and eight out of 14 (57%) D–J rearrangements remained stable. Using real-time quantitative PCR, a quantitative range 10^-4 was obtained in 64% of TCRB gene rearrangements and in 86% of cases a sensitivity 10^-4 was obtained. In conclusion, TCRB gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively stable and sensitive PCR targets for detection of minimal residual disease, particularly if this concerns complete V–(D)–J rearrangements.