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Detection of minimal residual disease in acute lymphoblastic leukemia by in
vitro amplification of rearranged T-cell receptor delta chain sequences
TE Hansen-Hagge, S Yokota and CR Bartram
Department of Pediatrics II, University of Ulm, FRG.
Human T-cell receptor (TCR) delta-chain diversity mainly originates from
high junctional variability, since only a limited number of germline
elements is available. This extraordinary diversity at the V.J junction,
due to the use of two D delta elements and extensive incorporation of N
nucleotides, constitutes a specific clonal marker for cell populations
exhibiting rearranged TCR delta genes. To this end we amplified in vitro by
polymerase chain reaction (PCR) the TCR delta junctional region of five
acute lymphoblastic leukemias (ALL), isolated respective DNA fragments, and
used them directly as clonospecific probes. The combination of PCR
technology and hybridization to clonospecific probes permitted the
detection of leukemia DNA at dilution of 1:100,000 in all five cases.
Moreover, we were able to investigate one of the ALL patients 11 months
after achieving continuous complete remission. Conventional Southern blot
analysis failed to detect rearranged TCR genes at this stage. However,
residual leukemic cells could readily be detected by PCR technique. We
conclude that the strategy proposed here is a very sensitive tool to detect
minimal residual disease in a significant proportion of human lymphoid
neoplasias.
Volume 74,
Issue 5,
pp. 1762-1767,
10/01/1989
Copyright © 1989 by The American Society of Hematology

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