Vdelta2-Jalpha 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 (precursor-B-ALL) are assumed to be mainly caused by Vdelta2-Jalpha rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vdelta2-Jalpha rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B-ALL. A significant proportion (44%) of Vdelta2-Jalpha rearrangements in childhood precursor-B-ALL were oligoclonal. Sequence analysis showed preferential usage of the Jalpha29 gene segment in 54% of rearrangements. The remaining Vdelta2-Jalpha rearrangements used 26 other Jalpha segments, which included 2 additional clusters, one involving the most upstream Jalpha segments (ie, Jalpha48 to Jalpha61; 23%) and the second cluster located around the Jalpha9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that Vdelta2 rearrangements to upstream Jalpha 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. Vdelta2-Jalpha29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal Vdelta2-Jalpha 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).
|Keywords||*Gene Rearrangement, Adolescent, Base Sequence, Child, Child, Preschool, Genes, T-Cell Receptor delta/*genetics, Humans, Infant, Leukemia, B-Cell, Acute/diagnosis/*genetics/pathology, Leukemia, Pre-B-Cell/diagnosis/*genetics/pathology, Lymphocytes, Molecular Diagnostic Techniques/methods/standards, Neoplasm, Residual/diagnosis/genetics, Polymerase Chain Reaction/methods, Research Support, Non-U.S. Gov't, Sensitivity and Specificity|
Szczepanski, T., van der Velden, V.H.J., Hoogeveen, P.G., de Bie, M., Jacobs, D.C., van Wering, E.R., & van Dongen, J.J.M.. (2004). Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells. Blood. Retrieved from http://hdl.handle.net/1765/8187