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Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population-based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002-2006

Thorn, Ingrid; Forestier, Erik; Thuresson, Britt LU ; Wasslavik, Carina; Malec, Maria; Li, Aihong; Lindstrom-Eriksson, Elenor; Botling, Johan; Barbany, Gisela and Jacobsson, Stefan, et al. (2010) In European Journal of Haematology1987-01-01+01:00 84(2). p.117-127
Abstract
Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements... (More)
Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (< 10-4) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T-ALL cases. With the stratification threshold of >= 10-3, which is applied in the current Nordic treatment protocol (NOPHO-ALL 2008) for the identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved. (Less)
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keywords
minimal residual disease, T-cell receptor genes, immunoglobulin, real-time quantitative polymerase chain reaction, rearranged, childhood acute lymphoblastic leukaemia
in
European Journal of Haematology1987-01-01+01:00
volume
84
issue
2
pages
117 - 127
publisher
Wiley-Blackwell
external identifiers
  • wos:000273301600004
  • scopus:74049121874
ISSN
1600-0609
DOI
10.1111/j.1600-0609.2009.01374.x
language
English
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yes
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c708e90a-62bc-4e51-99c3-73eb5cf79160 (old id 1533771)
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2010-01-27 14:52:23
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2018-05-29 10:42:46
@article{c708e90a-62bc-4e51-99c3-73eb5cf79160,
  abstract     = {Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (&lt; 10-4) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T-ALL cases. With the stratification threshold of &gt;= 10-3, which is applied in the current Nordic treatment protocol (NOPHO-ALL 2008) for the identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved.},
  author       = {Thorn, Ingrid and Forestier, Erik and Thuresson, Britt and Wasslavik, Carina and Malec, Maria and Li, Aihong and Lindstrom-Eriksson, Elenor and Botling, Johan and Barbany, Gisela and Jacobsson, Stefan and Olofsson, Tor and Porwit, Anna and Sundstrom, Christer and Rosenquist, Richard},
  issn         = {1600-0609},
  keyword      = {minimal residual disease,T-cell receptor genes,immunoglobulin,real-time quantitative polymerase chain reaction,rearranged,childhood acute lymphoblastic leukaemia},
  language     = {eng},
  number       = {2},
  pages        = {117--127},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology1987-01-01+01:00},
  title        = {Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population-based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002-2006},
  url          = {http://dx.doi.org/10.1111/j.1600-0609.2009.01374.x},
  volume       = {84},
  year         = {2010},
}