The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies 
in children with acute lymphoblastic leukaemia

Prospective studies in children with B‐precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)‐based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T‐cell receptor (TCR) gene rearrangements as targets can be used to identify patients wit...

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Veröffentlicht in:British journal of haematology 2002-01, Vol.116 (1), p.87-93
Hauptverfasser: De Haas, V., Breunis, W. B., Dee, R., Verhagen, O. J. H. M., Kroes, W., Van Wering, E. R., Van Dongen, J. J. M., Van Den Berg, H., Van Der Schoot, C. E.
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container_title British journal of haematology
container_volume 116
creator De Haas, V.
Breunis, W. B.
Dee, R.
Verhagen, O. J. H. M.
Kroes, W.
Van Wering, E. R.
Van Dongen, J. J. M.
Van Den Berg, H.
Van Der Schoot, C. E.
description Prospective studies in children with B‐precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)‐based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T‐cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse risk. The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL‐AML1 fusion gene is present in approximately 25% of children with B‐precursor ALL. In these patients, sensitive reverse transcription (RT)‐PCR analysis of the TEL‐AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow‐up. We investigated whether the MRD results obtained using RT‐PCR of TEL‐AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real‐time quantitative (RQ)‐PCR analysis for both types of targets and assessed the MRD levels in 36 follow‐up bone marrow samples (obtained during the first 1·5 years after diagnosis) from 13 patients with B‐precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ‐PCR and TEL‐AML1 RQ‐PCR revealed equal levels of MRD and these results had a strong correlation (P 
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The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL‐AML1 fusion gene is present in approximately 25% of children with B‐precursor ALL. In these patients, sensitive reverse transcription (RT)‐PCR analysis of the TEL‐AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow‐up. We investigated whether the MRD results obtained using RT‐PCR of TEL‐AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real‐time quantitative (RQ)‐PCR analysis for both types of targets and assessed the MRD levels in 36 follow‐up bone marrow samples (obtained during the first 1·5 years after diagnosis) from 13 patients with B‐precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ‐PCR and TEL‐AML1 RQ‐PCR revealed equal levels of MRD and these results had a strong correlation (P &lt; 0·0001, R2 = 0·84). Therefore, we conclude that the TEL‐AML1 RQ‐PCR can, in principle, replace Ig/TCR RQ‐PCR in B‐precursor ALL with t(12;21).</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.2002.03228.x</identifier><identifier>PMID: 11841400</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science, Ltd</publisher><subject>acute lymphoblastic leukaemia (ALL) ; Biological and medical sciences ; Child ; Computer Systems ; Core Binding Factor Alpha 2 Subunit ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte ; Genes, Immunoglobulin ; Hematologic and hematopoietic diseases ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Linear Models ; Medical sciences ; minimal residual disease (MRD) ; Neoplasm, Residual - diagnosis ; Oncogene Proteins, Fusion - genetics ; Polymerase Chain Reaction - methods ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis ; RNA, Messenger - analysis ; RQ‐PCR ; Sensitivity and Specificity ; TEL‐AML1 ; T‐cell receptor (TCR) genes</subject><ispartof>British journal of haematology, 2002-01, Vol.116 (1), p.87-93</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4458-3271805ccdcf3f44ca06fcd11a1f1c54ac2c1ef01fc21a833226c81b926af7fc3</citedby><cites>FETCH-LOGICAL-c4458-3271805ccdcf3f44ca06fcd11a1f1c54ac2c1ef01fc21a833226c81b926af7fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2141.2002.03228.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2141.2002.03228.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,4010,27900,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=13637463$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11841400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Haas, V.</creatorcontrib><creatorcontrib>Breunis, W. B.</creatorcontrib><creatorcontrib>Dee, R.</creatorcontrib><creatorcontrib>Verhagen, O. J. H. M.</creatorcontrib><creatorcontrib>Kroes, W.</creatorcontrib><creatorcontrib>Van Wering, E. R.</creatorcontrib><creatorcontrib>Van Dongen, J. J. M.</creatorcontrib><creatorcontrib>Van Den Berg, H.</creatorcontrib><creatorcontrib>Van Der Schoot, C. E.</creatorcontrib><title>The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies 
in children with acute lymphoblastic leukaemia</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Prospective studies in children with B‐precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)‐based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T‐cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse risk. The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL‐AML1 fusion gene is present in approximately 25% of children with B‐precursor ALL. In these patients, sensitive reverse transcription (RT)‐PCR analysis of the TEL‐AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow‐up. We investigated whether the MRD results obtained using RT‐PCR of TEL‐AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real‐time quantitative (RQ)‐PCR analysis for both types of targets and assessed the MRD levels in 36 follow‐up bone marrow samples (obtained during the first 1·5 years after diagnosis) from 13 patients with B‐precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ‐PCR and TEL‐AML1 RQ‐PCR revealed equal levels of MRD and these results had a strong correlation (P &lt; 0·0001, R2 = 0·84). Therefore, we conclude that the TEL‐AML1 RQ‐PCR can, in principle, replace Ig/TCR RQ‐PCR in B‐precursor ALL with t(12;21).</description><subject>acute lymphoblastic leukaemia (ALL)</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Computer Systems</subject><subject>Core Binding Factor Alpha 2 Subunit</subject><subject>Follow-Up Studies</subject><subject>Gene Rearrangement, T-Lymphocyte</subject><subject>Genes, Immunoglobulin</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Linear Models</subject><subject>Medical sciences</subject><subject>minimal residual disease (MRD)</subject><subject>Neoplasm, Residual - diagnosis</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</subject><subject>RNA, Messenger - analysis</subject><subject>RQ‐PCR</subject><subject>Sensitivity and Specificity</subject><subject>TEL‐AML1</subject><subject>T‐cell receptor (TCR) genes</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9uEzEQxlcIRNPCKyBfQHBIsNebzXLgUKKWgoJAKJwtZ3bcdfD-qe2lza2PwGPwUlz6JIxJRK-cZmT_vm_G_rKMCT4TvChfb2dClvNpLgoxyznPZ1zmeTW7eZBN_l08zCac88WUBNVRdhzClnMh-Vw8zo6EqApRcD7Jfq8bZOuz1d3tz9NPK8E8akd9tC2yq1F30UYd7Q9kQ-92LXodkEGjbZdIiLbv2Msvy6-vWGsvm0iHg9OALJJrEl9iAgGH2Huy3ZC8ZnTYtxYY6RgZgbOdBe3IorMtVY_B1iM1tQ2YBoY41hYDu7v9lfjGutqT8bWNDdMwRmS029D0G6dDJGOH43eNrdVPskdGu4BPD_Uk-3Z-tl5eTFef339Ynq6mUBTzairzhaj4HKAGI01RgOalgVoILYyAeaEhB4GGCwO50JWkzy6hEps3eanNwoA8yV7sfQffX40YomptAHROd9iPQS0EzSm4JLDag-D7EDwaNXh6s98pwVWKVm1VSlClBFWKVv2NVt2Q9Nlhxrhpsb4XHrIk4PkB0IG-03jdgQ33nCzloijTDm_33LV1uPvvBdS7jxepk38AW2bHvQ</recordid><startdate>200201</startdate><enddate>200201</enddate><creator>De Haas, V.</creator><creator>Breunis, W. B.</creator><creator>Dee, R.</creator><creator>Verhagen, O. J. H. M.</creator><creator>Kroes, W.</creator><creator>Van Wering, E. R.</creator><creator>Van Dongen, J. J. M.</creator><creator>Van Den Berg, H.</creator><creator>Van Der Schoot, C. E.</creator><general>Blackwell Science, Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200201</creationdate><title>The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies 
in children with acute lymphoblastic leukaemia</title><author>De Haas, V. ; Breunis, W. B. ; Dee, R. ; Verhagen, O. J. H. M. ; Kroes, W. ; Van Wering, E. R. ; Van Dongen, J. J. M. ; Van Den Berg, H. ; Van Der Schoot, C. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4458-3271805ccdcf3f44ca06fcd11a1f1c54ac2c1ef01fc21a833226c81b926af7fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>acute lymphoblastic leukaemia (ALL)</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Computer Systems</topic><topic>Core Binding Factor Alpha 2 Subunit</topic><topic>Follow-Up Studies</topic><topic>Gene Rearrangement, T-Lymphocyte</topic><topic>Genes, Immunoglobulin</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Linear Models</topic><topic>Medical sciences</topic><topic>minimal residual disease (MRD)</topic><topic>Neoplasm, Residual - diagnosis</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</topic><topic>RNA, Messenger - analysis</topic><topic>RQ‐PCR</topic><topic>Sensitivity and Specificity</topic><topic>TEL‐AML1</topic><topic>T‐cell receptor (TCR) genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Haas, V.</creatorcontrib><creatorcontrib>Breunis, W. B.</creatorcontrib><creatorcontrib>Dee, R.</creatorcontrib><creatorcontrib>Verhagen, O. J. H. M.</creatorcontrib><creatorcontrib>Kroes, W.</creatorcontrib><creatorcontrib>Van Wering, E. R.</creatorcontrib><creatorcontrib>Van Dongen, J. J. M.</creatorcontrib><creatorcontrib>Van Den Berg, H.</creatorcontrib><creatorcontrib>Van Der Schoot, C. E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Haas, V.</au><au>Breunis, W. B.</au><au>Dee, R.</au><au>Verhagen, O. J. H. M.</au><au>Kroes, W.</au><au>Van Wering, E. R.</au><au>Van Dongen, J. J. M.</au><au>Van Den Berg, H.</au><au>Van Der Schoot, C. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies 
in children with acute lymphoblastic leukaemia</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2002-01</date><risdate>2002</risdate><volume>116</volume><issue>1</issue><spage>87</spage><epage>93</epage><pages>87-93</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Prospective studies in children with B‐precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)‐based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T‐cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse risk. The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL‐AML1 fusion gene is present in approximately 25% of children with B‐precursor ALL. In these patients, sensitive reverse transcription (RT)‐PCR analysis of the TEL‐AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow‐up. We investigated whether the MRD results obtained using RT‐PCR of TEL‐AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real‐time quantitative (RQ)‐PCR analysis for both types of targets and assessed the MRD levels in 36 follow‐up bone marrow samples (obtained during the first 1·5 years after diagnosis) from 13 patients with B‐precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ‐PCR and TEL‐AML1 RQ‐PCR revealed equal levels of MRD and these results had a strong correlation (P &lt; 0·0001, R2 = 0·84). Therefore, we conclude that the TEL‐AML1 RQ‐PCR can, in principle, replace Ig/TCR RQ‐PCR in B‐precursor ALL with t(12;21).</abstract><cop>Oxford, UK</cop><pub>Blackwell Science, Ltd</pub><pmid>11841400</pmid><doi>10.1046/j.1365-2141.2002.03228.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects acute lymphoblastic leukaemia (ALL)
Biological and medical sciences
Child
Computer Systems
Core Binding Factor Alpha 2 Subunit
Follow-Up Studies
Gene Rearrangement, T-Lymphocyte
Genes, Immunoglobulin
Hematologic and hematopoietic diseases
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Linear Models
Medical sciences
minimal residual disease (MRD)
Neoplasm, Residual - diagnosis
Oncogene Proteins, Fusion - genetics
Polymerase Chain Reaction - methods
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
RNA, Messenger - analysis
RQ‐PCR
Sensitivity and Specificity
TEL‐AML1
T‐cell receptor (TCR) genes
title The TEL‐AML1 real‐time quantitative polymerase chain reaction (PCR) might replace the antigen receptor‐based genomic PCR in clinical minimal residual disease studies 
in children with acute lymphoblastic leukaemia
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