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Use of polymerase chain reactions to monitor minimal residual disease in
acute lymphoblastic leukemia patients
S Yokota, TE Hansen-Hagge, WD Ludwig, A Reiter, A Raghavachar, E Kleihauer and CR Bartram
Department of Pediatrics II, University of Ulm, Germany.
T-cell receptor (TCR) delta gene rearrangements are observed in more than
80% of acute lymphoblastic leukemia (ALL) patients. Moreover, a
preferential usage of specific genetic elements has been shown in different
ALL subtypes: V delta 1 DJ delta 1 rearrangements predominate in T-ALL,
while most B-precursor ALLs show a recombination of V delta 2 to D delta 3.
Recently we have proposed a strategy for the detection of minimal residual
disease (MRD) based on the isolation of clonospecific probes following the
in vitro amplification of V delta 1 DJ delta 1 junctions by polymerase
chain reaction (PCR) and now have adapted this method to the preparation of
specific V delta 2 D delta 3 fragments. In the present study, clonospecific
probes were generated from 11 T-ALL and 16 cALL patients (21 children, 6
adults). The sensitivity of these 27 probes in detecting residual leukemia
cells varied between 10(-4) to 10(-6) as determined by semiquantitative
evaluation of dilution experiments. PCR analysis of 55 bone marrow (BM) and
peripheral blood (PB) samples obtained from the 27 patients during complete
clinical remission showed the following results: (1) Evidence for MRD was
obtained in the BM of all patients (eight of eight) investigated 2 to 6
months after remission induction and also in 6 of 11 cases on maintenance
therapy 7 to 19 months after diagnosis. (2) In contrast, all patients but
one (10 of 11) analyzed 6 to 41 months after the termination of treatment
lacked apparent evidence for leukemia DNA; the exception was a girl
exhibiting 10(-4) to 10(-5) residual cells in her PB 5.5 years after
diagnosis. (3) Longitudinal analysis in nine patients disclosed marked
individual differences in the intervals between achievement of clinical
remission and complete eradication of the leukemia cell clone. (4)
Differences in the duration of MRD were not associated with distinct
clinical-hematologic features. (5) Detection of residual disease by PCR
proceeded clinical relapse in two cases.
Volume 77,
Issue 2,
pp. 331-339,
01/15/1991
Copyright © 1991 by The American Society of Hematology
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