IMMUNOBIOLOGY V 2-J rearrangements are frequent in precursor-B–acute lymphoblastic leukemia but rare in normal lymphoid cells

The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B– acute lymphoblastic leukemia (precursorB–ALL) are assumed to be mainly caused by V 2-J rearrangements. We designed a multiplex polymerase chain reaction (PCR) assay with 61 J primers and identified clonal V 2-J rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B–ALL. A significant proportion (44%) of V 2-J rearrangements in childhood precursor-B– ALL were oligoclonal. Sequence analysis showed preferential usage of the J 29 gene segment in 54% of rearrangements. The remaining V 2-J rearrangements used 26 other J segments, which included 2 additional clusters, one involving the most upstream J segments (ie, J 48 to J 61; 23%) and the second cluster located around the J 9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that V 2 rearrangements to upstream J 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. V 2-J 29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal V 2-J 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). (Blood. 2004;103:3798-3804)