Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection
Issue date
2003Author
Li, Aihong
Zhou, Jianbiao
Zuckerman, David
Dalton, Virginia
Lyons, Cheryl
Silverman, Lewis B.
Sallan, Stephen E.
Gribben, John G.
Suggested citation
Li, Aihong;
Zhou, Jianbiao;
Zuckerman, David;
Dalton, Virginia;
Lyons, Cheryl;
Silverman, Lewis B.;
...
Rué i Monné, Montserrat.
(2003)
.
Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection.
Blood, 2003, vol. 102, núm. 13, p. 4520-4526.
https://doi.org/10.1182/blood-2003-05-1455.
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Show full item recordAbstract
Immunoglobulin (Ig) and T-cell receptor
(TCR) gene rearrangements provide clonal
markers useful for diagnosis and measurement
of minimal residual disease
(MRD) in acute lymphoblastic leukemia
(ALL). We analyzed the sequences of Ig
and TCR gene rearrangements obtained
at presentation and relapse in 41 children
with ALL to study clonal stability, which
has important implications for monitoring
MRD, during the course of the disease.
In 42%, all original Ig and/or TCR
sequences were conserved. In 24%, one
original sequence was preserved but the
other lost, and in 14% the original sequences
were conserved with new sequences
identified at relapse. In 20% only
new sequences were found at relapse.
Using primers designed from the novel
relapse sequences, the relapse clone
could be identified as subdominant clones
in the diagnostic sample in 8 of 14 patients.
Alteration of these clonal gene
rearrangements is a common feature in
childhood ALL. MRD detection should
include multiple gene targets to minimize
false-negative samples or include also
multicolor flow cytometry. In some cases
the leukemic progenitor cell might arise
earlier in lineage before DHJH recombination
but retain the capacity to further
differentiate into cells capable of altering
the pattern of Ig and/or TCR rearrangements.