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T-cell receptor delta gene recombination in common acute lymphoblastic
leukemia: preferential usage of V delta 2 and frequent involvement of the J
alpha cluster
S Yokota, TE Hansen-Hagge and CR Bartram
Department of Pediatrics II, University of Ulm, FRG.
A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL)
exhibit a recombination of the T-cell receptor (TCR) delta chain locus.
Interestingly, distinct TCR delta elements are preferentially used in
immunologic subtypes. In a recent series of 201 children with common ALL
(cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the
latter showing a hybridization pattern in Southern blots suggestive of a V
delta 2 to D delta 3 recombination. To verify this interpretation and to
elucidate in more detail the diversity of this common type of TCR delta
recombination we amplified and sequenced the junctional region of nine cALL
patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta
2 D delta 3 recombination was confirmed in all cases; convincing evidence
for the participation of D delta 1 or D delta 2 elements was not obtained.
Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries
within V delta 2 D delta 3 segments, a limitation of junctional diversity
also detected in 50% of peripheral blood cell clones derived from two
healthy probands. Notably, sequence identity at the V delta 2 D delta 3
junction was demonstrated for a cALL and one of the control clones. Another
group of 35 of 162 cALL patients was characterized by V delta 2
rearrangements and biallelic deletion of J delta and C delta sequences.
Using a J alpha consensus primer, PCR-directed sequence analysis
demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases
analyzed by this approach. The J alpha segments of these patients differed,
but were identical or homologous to published J alpha elements. Our data
suggest a recombination pathway of the TCR delta/alpha locus leading to
chimeric TCR alpha molecules, containing V delta and, remarkably, also D
delta sequences.
Volume 77,
Issue 1,
pp. 141-148,
01/01/1991
Copyright © 1991 by The American Society of Hematology
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