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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3798-3804.
Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-08-2952.


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IMMUNOBIOLOGY

V{delta}2-J{alpha} rearrangements are frequent in precursor-B–acute lymphoblastic leukemia but rare in normal lymphoid cells

Tomasz Szczepanski, Vincent H. J. van der Velden, Patricia G. Hoogeveen, Maaike de Bie, Daniëlle C. H. Jacobs, Elisabeth R. van Wering, and Jacques J. M. van Dongen

From the Department of Immunology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Pediatric Hematology and Oncology, Silesian Medical Academy, Zabrze, Poland; and Dutch Childhood Oncology Group, The Hague, the Netherlands.

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 V{delta}2-J{alpha} rearrangements. We designed a multiplex polymerase chain reaction tified clonal V{delta}2-J{alpha} rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B–ALL. A significant proportion (44%) of V{delta}2-J{alpha} rearrangements in childhood precursor-B–ALL were oligoclonal. Sequence analysis showed preferential usage of the J{alpha}29 gene segment in 54% of rearrangements. The remaining V{delta}2-J{alpha} rearrangements used 26 other J{alpha} segments, which included 2 additional clusters, one involv ing the most upstream J{alpha} segments (ie, J{alpha}48 to J{alpha}61; 23%) and the second cluster located around the J{alpha}9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that V{delta}2 rearrangements to upstream J{alpha} 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{delta}2-J{alpha}29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal V{delta}2-J{alpha} 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).


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