 visitant ::
identificació
|
|||||||||||||||
|
Cerca | Lliura | Ajuda | Servei de Biblioteques | Sobre el DDD | Català English Español | |||||||||
| Pàgina inicial > Articles > Articles publicats > A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia |
(Institut d'Investigació Biomèdica Sant Pau) (Hospital Universitario Ramón y Cajal (Madrid)) (Hospital Universitari i Politècnic La Fe (València)) (Hospital Clínico San Carlos (Madrid)) (Institut d'Investigació Biomèdica Sant Pau) (Centro Nacional de Investigaciones Oncológicas)| Data: | 2019 |
| Resum: | 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 for single nucleotide variants and 10 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. |
| Ajuts: | Ministerio de Economía y Competitividad PI13/02387 Ministerio de Economía y Competitividad PI16/01530 Ministerio de Economía y Competitividad FPDI-2013-16409 Ministerio de Economía y Competitividad IFI 14/00008 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Haematologica, Vol. 104 Núm. 2 (31 2019) , p. 288-296, ISSN 1592-8721 |
