RT Journal Article
T1 A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
A1 Onecha. Esther, 
A1 Linares Gómez, María
A1 Rapado, Inmaculada
A1 Ruiz-Heredia, Yanira
A1 Martínez Sánchez, María Del Pilar
A1 Cedena Romero, M. Teresa
A1 Pratcorona, Marta
A1 Perez Oteyza, Jaime
A1 Herrera, Pilar
A1 Barragan, Eva
A1 Montesinos, Pau
A1 Garcia Vela, Jose Antonio
A1 Magro, Elena
A1 Anguita Mandly, Eduardo Luis
A1 Figuera, Angela
A1 Riaza, Rosalia
A1 Martínez Barranco, María Pilar
A1 Sanchez-Vega, Beatriz
A1 Nomdedeu, Josep
A1 Gallardo, Miguel
A1 Ayala Díaz, Rosa María
A1 Martínez López, Joaquín
AB A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10−4 for single nucleotide variants and 10−5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing–determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P<0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, P=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, P=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.
PB Ferrata Storti Foundation
SN 0390-6078
YR 2019
FD 2019-02
LK https://hdl.handle.net/20.500.14352/93581
UL https://hdl.handle.net/20.500.14352/93581
LA eng
NO Onecha E, Linares M, Rapado I, Ruiz-Heredia Y, Martinez-Sanchez P, Cedena T, et al. A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia. Haematologica 2019;104:288–96. https://doi.org/10.3324/haematol.2018.194712.
NO Instituto de Salud Carlos III: Subdirección General de Investigación Sanitaria
NO Fundación CRIS contra el cáncer
NO Ministerio de Economía, Comercio y Empresa (España)
DS Docta Complutense
RD 12 abr 2025