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Next‐generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3 ‐ITD or NPM1 mutations
Author(s) -
Thol Felicitas,
Kölking Britta,
Damm Frederik,
Reinhardt Katarina,
Klusmann JanHenning,
Reinhardt Dirk,
von Neuhoff Nils,
Brugman Martijn H.,
Schlegelberger Brigitte,
Suerbaum Sebastian,
Krauter Jürgen,
Ganser Arnold,
Heuser Michael
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21955
Subject(s) - npm1 , minimal residual disease , myeloid leukemia , dna sequencing , dominance (genetics) , biology , oncology , polymerase chain reaction , leukemia , medicine , genetics , computational biology , cancer research , dna , gene , chromosome , karyotype
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.