Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.

Next-Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has establis...

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Autores: Sargas C, Ayala R, Larráyoz MJ, Chillón MC, Carrillo-Cruz E, Bilbao-Sieyro C, Prados de la Torre E, Martínez-Cuadrón D, Rodríguez-Veiga R, Boluda B, Gil C, Bernal T, Bergua JM, Algarra L, Tormo M, Martínez-Sánchez P, Soria E, Serrano J, Alonso-Domínguez JM, García-Boyero R, Amigo ML, Herrera-Puente P, Sayas MJ, Lavilla-Rubira E, Martínez-López J, Calasanz MJ, García-Sanz R, Pérez-Simón JA, Gómez-Casares MT, Sánchez-García J, Barragán E, Montesinos P
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p9484
Acesso em linha:https://isabial.portalinvestigacion.com/publicaciones9484
Access Level:acceso abierto
Palavra-chave:Next–Generation Sequencing
acute myeloid leukemia
clinical validation
cross–validations
genomic classification
mutational profile
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spelling Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.Sargas CAyala RLarráyoz MJChillón MCCarrillo-Cruz EBilbao-Sieyro CPrados de la Torre EMartínez-Cuadrón DRodríguez-Veiga RBoluda BGil CBernal TBergua JMAlgarra LTormo MMartínez-Sánchez PSoria ESerrano JAlonso-Domínguez JMGarcía-Boyero RAmigo MLHerrera-Puente PSayas MJLavilla-Rubira EMartínez-López JCalasanz MJGarcía-Sanz RPérez-Simón JAGómez-Casares MTSánchez-García JBarragán EMontesinos PNext–Generation Sequencingacute myeloid leukemiaclinical validationcross–validationsgenomic classificationmutational profileNext-Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has established the first nationwide diagnostic network of seven reference laboratories to provide standardized NGS studies for AML patients. Cross-validation (CV) rounds are regularly performed to ensure the quality of NGS studies and to keep updated clinically relevant genes recommended for NGS study. The molecular characterization of 2856 samples (1631 derived from the NGS-AML project; NCT03311815) with standardized NGS of consensus genes (ABL1, ASXL1, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1) showed 97% of patients having at least one mutation. The mutational profile was highly variable according to moment of disease, age and sex, and several co-occurring and exclusion relations were detected. Molecular testing based on NGS allowed accurate diagnosis and reliable prognosis stratification of 954 AML patients according to new genomic classification proposed by Tazi et al. Novel molecular subgroups, such as mutated WT1 and mutations in at least two myelodysplasia-related genes, have been associated with an adverse prognosis in our cohort. In this way, the PETHEMA cooperative group efficiently provides an extensive molecular characterization for AML diagnosis and risk stratification, ensuring technical quality and equity in access to NGS studies.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones9484CancersISSN: 20726694reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p94842026-06-12T10:20:37Z
dc.title.none.fl_str_mv Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
title Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
spellingShingle Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
Sargas C
Next–Generation Sequencing
acute myeloid leukemia
clinical validation
cross–validations
genomic classification
mutational profile
title_short Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
title_full Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
title_fullStr Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
title_full_unstemmed Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
title_sort Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry.
dc.creator.none.fl_str_mv Sargas C
Ayala R
Larráyoz MJ
Chillón MC
Carrillo-Cruz E
Bilbao-Sieyro C
Prados de la Torre E
Martínez-Cuadrón D
Rodríguez-Veiga R
Boluda B
Gil C
Bernal T
Bergua JM
Algarra L
Tormo M
Martínez-Sánchez P
Soria E
Serrano J
Alonso-Domínguez JM
García-Boyero R
Amigo ML
Herrera-Puente P
Sayas MJ
Lavilla-Rubira E
Martínez-López J
Calasanz MJ
García-Sanz R
Pérez-Simón JA
Gómez-Casares MT
Sánchez-García J
Barragán E
Montesinos P
author Sargas C
author_facet Sargas C
Ayala R
Larráyoz MJ
Chillón MC
Carrillo-Cruz E
Bilbao-Sieyro C
Prados de la Torre E
Martínez-Cuadrón D
Rodríguez-Veiga R
Boluda B
Gil C
Bernal T
Bergua JM
Algarra L
Tormo M
Martínez-Sánchez P
Soria E
Serrano J
Alonso-Domínguez JM
García-Boyero R
Amigo ML
Herrera-Puente P
Sayas MJ
Lavilla-Rubira E
Martínez-López J
Calasanz MJ
García-Sanz R
Pérez-Simón JA
Gómez-Casares MT
Sánchez-García J
Barragán E
Montesinos P
author_role author
author2 Ayala R
Larráyoz MJ
Chillón MC
Carrillo-Cruz E
Bilbao-Sieyro C
Prados de la Torre E
Martínez-Cuadrón D
Rodríguez-Veiga R
Boluda B
Gil C
Bernal T
Bergua JM
Algarra L
Tormo M
Martínez-Sánchez P
Soria E
Serrano J
Alonso-Domínguez JM
García-Boyero R
Amigo ML
Herrera-Puente P
Sayas MJ
Lavilla-Rubira E
Martínez-López J
Calasanz MJ
García-Sanz R
Pérez-Simón JA
Gómez-Casares MT
Sánchez-García J
Barragán E
Montesinos P
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Next–Generation Sequencing
acute myeloid leukemia
clinical validation
cross–validations
genomic classification
mutational profile
topic Next–Generation Sequencing
acute myeloid leukemia
clinical validation
cross–validations
genomic classification
mutational profile
description Next-Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has established the first nationwide diagnostic network of seven reference laboratories to provide standardized NGS studies for AML patients. Cross-validation (CV) rounds are regularly performed to ensure the quality of NGS studies and to keep updated clinically relevant genes recommended for NGS study. The molecular characterization of 2856 samples (1631 derived from the NGS-AML project; NCT03311815) with standardized NGS of consensus genes (ABL1, ASXL1, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1) showed 97% of patients having at least one mutation. The mutational profile was highly variable according to moment of disease, age and sex, and several co-occurring and exclusion relations were detected. Molecular testing based on NGS allowed accurate diagnosis and reliable prognosis stratification of 954 AML patients according to new genomic classification proposed by Tazi et al. Novel molecular subgroups, such as mutated WT1 and mutations in at least two myelodysplasia-related genes, have been associated with an adverse prognosis in our cohort. In this way, the PETHEMA cooperative group efficiently provides an extensive molecular characterization for AML diagnosis and risk stratification, ensuring technical quality and equity in access to NGS studies.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones9484
url https://isabial.portalinvestigacion.com/publicaciones9484
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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