Vδ2-Jα rearrangements are frequent in precursor-B–acute lymphoblastic leukemia but rare in normal lymphoid cells

Abstract

AbstractThe frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B–acute lymphoblastic leukemia (precursor-B–ALL) are assumed to be mainly caused by Vδ2-Jα rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vδ2-Jα rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B–ALL. A significant proportion (44%) of Vδ2-Jα rearrangements in childhood precursor-B–ALL were oligoclonal. Sequence analysis showed preferential usage of the Jα29 gene segment in 54% of rearrangements. The remaining Vδ2-Jα rearrangements used 26 other Jα segments, which included 2 additional clusters, one involv ing the most upstream Jα segments (ie, Jα48 to Jα61; 23%) and the second cluster located around the Jα9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that Vδ2 rearrangements to upstream Jα segments occurred at low levels in the thymus (10–2 to 10–3) and were rare (generally below 10–3) in B-cell precursors and mature T cells. Vδ2-Jα29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal Vδ2-Jα rearrangements in precursor-B–ALL may serve as patient-specific targets for detection of minimal residual disease, because they show high sensitivity (10–4 or less in most cases) and good stability (88% of rearrangements preserved at relapse).