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 Previous Article | Table of Contents | Next Article 
Analysis of Ig and T-cell receptor genes in 40 childhood acute
lymphoblastic leukemias at diagnosis and subsequent relapse: implications
for the detection of minimal residual disease by polymerase chain reaction
analysis
A Beishuizen, MA Verhoeven, ER van Wering, K Hahlen, H Hooijkaas and JJ van Dongen
Department of Immunology, Erasmus University/University Hospital Dijkzigt,
Rotterdam, The Netherlands.
The rearrangement patterns of Ig and T-cell receptor (TcR) genes were
studied by Southern blot analysis in 30 precursor B-cell acute
lymphoblastic leukemias (B-ALLs) and 10 T-ALLs at diagnosis and subsequent
relapse. Eight precursor B-ALLs appeared to contain biclonal/oligoclonal Ig
heavy-chain (IgH) gene rearrangements at diagnosis. Differences in
rearrangement patterns between diagnosis and relapse were found in 67% (20
cases) of precursor B-ALLs (including all eight biclonal/oligoclonal cases)
and 50% (five cases) of T-ALLs. In precursor B-ALLs, especially changes in
IgH and/or TcR-delta gene rearrangements were found (17 cases), but also
changes in TcR-beta, TcR- gamma, Ig kappa, and/or Ig lambda genes (11
cases) occurred. The changes in T-ALLs concerned the TcR-beta, TcR-gamma,
TcR-delta, and/or IgH genes. Two precursor B-ALLs showed completely
different Ig and TcR gene rearrangement patterns at relapse, suggesting the
absence of a clonal relation between the leukemic cells at diagnosis and
relapse and the development of a secondary leukemia. The clonal evolution
in the other 23 ALL patients was based on continuing rearrangement
processes and selection of subclones. The development of changes in Ig and
TcR gene rearrangement patterns was related to remission duration,
suggesting an increasing chance of continuing rearrangement processes with
time. These immunogenotypic changes at relapse occurred in a hierarchical
order, with changes in IgH and TcR-delta genes occurring after only 6
months of remission duration, whereas changes in other Ig and TcR genes
were generally detectable after 1 to 2 years of remission duration. The
heterogeneity reported here in Ig and/or TcR gene rearrangement patterns at
diagnosis and relapse might hamper polymerase chain reaction (PCR)-mediated
detection of minimal residual disease (MRD) using junctional regions of
rearranged Ig or TcR genes as PCR targets. However, our data also indicate
that in 75% to 90% of ALLs, at least one major rearranged IgH, TcR-gamma,
or TcR-delta band (allele) remained stable at relapse. We conclude that two
or more junctional regions of different genes (IgH, TcR-gamma, and/or
TcR-delta) should be monitored during follow-up of ALL patients for MRD
detection by use of PCR techniques. Especially in biclonal/oligoclonal
precursor B-ALL cases, the monitoring should not be restricted to
rearranged IgH genes, but TcR-gamma and/or TcR-delta genes should be
monitored as well, because of the extensive changes in IgH gene
rearrangement patterns in this ALL subgroup.
Volume 83,
Issue 8,
pp. 2238-2247,
04/15/1994
Copyright © 1994 by The American Society of Hematology
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