Unexpected consistent involvement of V beta gene segments in inappropriate
T-cell receptor beta gene rearrangements occurring in B- lineage acute
lymphoblastic leukemias
H Dombret, P Loiseau, JC Bories and F Sigaux
Laboratory of Molecular Hematology, Saint-Louis Hospital, Paris, France.
T-cell receptor beta (TCR beta) gene rearrangements occur in a third of
early B-cell acute lymphoblastic leukemias (ALLs). V, D, and J segments
involved in these inappropriate rearrangements remain unknown and are of
interest, both because partial D beta J beta and complete V beta D beta J
beta recombinations occur at distinct stages of thymic maturation and
because these rearrangements are regulated differently. We have therefore
studied in detail seven cases of B-lineage ALL that show inappropriate
clonal TCR beta gene rearrangements. Analysis of genomic DNA by Southern
hybridization with C beta, J beta 1, V beta 8, and V beta 11 probes
suggested the involvement of V beta segment in tumor cell rearrangements. A
complete genomic library constructed from one case was screened with a C
beta probe, and the TCR beta gene rearrangement was cloned and fully
sequenced to show an out of frame V beta 2.2-J beta 2.6 recombination. TCR
beta gene rearrangements occurring in other cases were further analyzed by
polymerase chain reaction (PCR) using J beta and V beta primers and the
resulting specific PCR products were sequenced. Evidence of clonal V beta
rearrangements was obtained in all cases. These unexpected findings
represent the first definitive demonstration that complete V beta(D beta)J
beta rearrangements can occur in B-lineage cells and contrast with the
previously reported lack of V beta(D beta)J beta rearrangement in B cells
from V beta-J beta-C beta-E mu transgenic mice. In the context of
increasing evidence that rearrangements are linked to transcription of
unrearranged gene segments, these data prompt a search in B-lineage ALL
cells for the presence of germline V beta transcripts whose deregulated
expression may be linked to early transforming events.
Volume 80,
Issue 10,
pp. 2614-2621,
11/15/1992
Copyright © 1992 by The American Society of Hematology
