Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations
Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next‐generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of N...
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| Veröffentlicht in: | Genes chromosomes & cancer 2012-07, Vol.51 (7), p.689-695 |
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| creator | Thol, Felicitas Kölking, Britta Damm, Frederik Reinhardt, Katarina Klusmann, Jan-Henning Reinhardt, Dirk von Neuhoff, Nils Brugman, Martijn H. Schlegelberger, Brigitte Suerbaum, Sebastian Krauter, Jürgen Ganser, Arnold Heuser, Michael |
| description | Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next‐generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3‐internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3‐ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real‐time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. © 2012 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/gcc.21955 |
| format | Article |
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We evaluated next‐generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3‐internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3‐ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real‐time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. © 2012 Wiley Periodicals, Inc.</description><identifier>ISSN: 1045-2257</identifier><identifier>EISSN: 1098-2264</identifier><identifier>DOI: 10.1002/gcc.21955</identifier><identifier>PMID: 22454318</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Alleles ; Child ; fms-Like Tyrosine Kinase 3 - genetics ; Humans ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Mutation ; Neoplasm, Residual - genetics ; Nuclear Proteins - genetics ; Sensitivity and Specificity ; Sequence Analysis, DNA - methods ; Tandem Repeat Sequences</subject><ispartof>Genes chromosomes & cancer, 2012-07, Vol.51 (7), p.689-695</ispartof><rights>Copyright © 2012 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3635-fb6c4fd043f98d9ea2e43c5c561ca4d4e891ffec6da17fbca32e0380a339d2b23</citedby><cites>FETCH-LOGICAL-c3635-fb6c4fd043f98d9ea2e43c5c561ca4d4e891ffec6da17fbca32e0380a339d2b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fgcc.21955$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fgcc.21955$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22454318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thol, Felicitas</creatorcontrib><creatorcontrib>Kölking, Britta</creatorcontrib><creatorcontrib>Damm, Frederik</creatorcontrib><creatorcontrib>Reinhardt, Katarina</creatorcontrib><creatorcontrib>Klusmann, Jan-Henning</creatorcontrib><creatorcontrib>Reinhardt, Dirk</creatorcontrib><creatorcontrib>von Neuhoff, Nils</creatorcontrib><creatorcontrib>Brugman, Martijn H.</creatorcontrib><creatorcontrib>Schlegelberger, Brigitte</creatorcontrib><creatorcontrib>Suerbaum, Sebastian</creatorcontrib><creatorcontrib>Krauter, Jürgen</creatorcontrib><creatorcontrib>Ganser, Arnold</creatorcontrib><creatorcontrib>Heuser, Michael</creatorcontrib><title>Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations</title><title>Genes chromosomes & cancer</title><addtitle>Genes Chromosom. Cancer</addtitle><description>Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next‐generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3‐internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3‐ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real‐time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. © 2012 Wiley Periodicals, Inc.</description><subject>Adult</subject><subject>Alleles</subject><subject>Child</subject><subject>fms-Like Tyrosine Kinase 3 - genetics</subject><subject>Humans</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Mutation</subject><subject>Neoplasm, Residual - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Sensitivity and Specificity</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Tandem Repeat Sequences</subject><issn>1045-2257</issn><issn>1098-2264</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtuEzEUhi0EoqWw4AWQl7CY1te5LFGgaaUQsghCYmM59nEwnfEE26M2D8B712na7lj5l_Wd7-j8CL2n5JwSwi62xpwz2kn5Ap1S0rUVY7V4echCliybE_QmpT-EkJp38jU6YUxIwWl7iv4t4S5XWwgQdfZjwAn-ThCMD1vsxogHH_ygexwheTuVYH0CnQAPY_B5jAfOB6zNlMvfHvrRW9zDdAOD13hXnBBywrc-_8aXizWvrtdfcPEuV98oHqb8sDS9Ra-c7hO8e3zP0I_Lr-vZVbX4Pr-efV5UhtdcVm5TG-EsEdx1re1AMxDcSCNrarSwAtqOOgemtpo2bmM0Z0B4SzTnnWUbxs_Qx6N3F8dyZspq8MlA3-sA45QUJZS2ghFaF_TTETVxTCmCU7tYmoj7AqlD66q0rh5aL-yHR-20GcA-k081F-DiCNz6Hvb_N6n5bPakrI4TPmW4e57Q8UbVDW-k-rmcq1W3IuRXw5Xk9wzznNY</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Thol, Felicitas</creator><creator>Kölking, Britta</creator><creator>Damm, Frederik</creator><creator>Reinhardt, Katarina</creator><creator>Klusmann, Jan-Henning</creator><creator>Reinhardt, Dirk</creator><creator>von Neuhoff, Nils</creator><creator>Brugman, Martijn H.</creator><creator>Schlegelberger, Brigitte</creator><creator>Suerbaum, Sebastian</creator><creator>Krauter, Jürgen</creator><creator>Ganser, Arnold</creator><creator>Heuser, Michael</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>201207</creationdate><title>Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations</title><author>Thol, Felicitas ; Kölking, Britta ; Damm, Frederik ; Reinhardt, Katarina ; Klusmann, Jan-Henning ; Reinhardt, Dirk ; von Neuhoff, Nils ; Brugman, Martijn H. ; Schlegelberger, Brigitte ; Suerbaum, Sebastian ; Krauter, Jürgen ; Ganser, Arnold ; Heuser, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3635-fb6c4fd043f98d9ea2e43c5c561ca4d4e891ffec6da17fbca32e0380a339d2b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Child</topic><topic>fms-Like Tyrosine Kinase 3 - genetics</topic><topic>Humans</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Mutation</topic><topic>Neoplasm, Residual - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Sensitivity and Specificity</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Tandem Repeat Sequences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thol, Felicitas</creatorcontrib><creatorcontrib>Kölking, Britta</creatorcontrib><creatorcontrib>Damm, Frederik</creatorcontrib><creatorcontrib>Reinhardt, Katarina</creatorcontrib><creatorcontrib>Klusmann, Jan-Henning</creatorcontrib><creatorcontrib>Reinhardt, Dirk</creatorcontrib><creatorcontrib>von Neuhoff, Nils</creatorcontrib><creatorcontrib>Brugman, Martijn H.</creatorcontrib><creatorcontrib>Schlegelberger, Brigitte</creatorcontrib><creatorcontrib>Suerbaum, Sebastian</creatorcontrib><creatorcontrib>Krauter, Jürgen</creatorcontrib><creatorcontrib>Ganser, Arnold</creatorcontrib><creatorcontrib>Heuser, Michael</creatorcontrib><collection>Istex</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>Genes chromosomes & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thol, Felicitas</au><au>Kölking, Britta</au><au>Damm, Frederik</au><au>Reinhardt, Katarina</au><au>Klusmann, Jan-Henning</au><au>Reinhardt, Dirk</au><au>von Neuhoff, Nils</au><au>Brugman, Martijn H.</au><au>Schlegelberger, Brigitte</au><au>Suerbaum, Sebastian</au><au>Krauter, Jürgen</au><au>Ganser, Arnold</au><au>Heuser, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations</atitle><jtitle>Genes chromosomes & cancer</jtitle><addtitle>Genes Chromosom. 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| ispartof | Genes chromosomes & cancer, 2012-07, Vol.51 (7), p.689-695 |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Adult Alleles Child fms-Like Tyrosine Kinase 3 - genetics Humans Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Mutation Neoplasm, Residual - genetics Nuclear Proteins - genetics Sensitivity and Specificity Sequence Analysis, DNA - methods Tandem Repeat Sequences |
| title | Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations |
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