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

Abstract

The 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 polymerese chain reaction (PCR) assay with 61 Jα primers and identified 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 involving the most upstream Jα segments (le, Jα48 to Jα61; 23%) and the second cluster located around the Jα9 gene segment (7%). Real-time quantitative PCR studies of normal lymphold 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). © 2004 by The American Society of Hematology.