Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA Registry
Simple Summary Next-Generation Sequencing (NGS) has provided a deeper genetic understanding of acute myeloid leukemia (AML) that has been recently incorporated into AML classification and risk-stratification guidelines. Single molecular analysis has become inefficient and molecular testing based on...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p17130 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/17130 |
| Access Level: | acceso abierto |
| Palabra clave: | acute myeloid leukemia Next-Generation Sequencing cross-validations mutational profile genomic classification clinical validation |
| id |
ES_bf3d1485a33a282cab2b334054ef3caa |
|---|---|
| oai_identifier_str |
oai:incliva.fundanetsuite.com:p17130 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Molecular Landscape and Validation of New Genomic Classification in 2668 Adult AML Patients: Real Life Data from the PETHEMA RegistrySargas, ClaudiaAyala, RosaLarrayoz, Maria JoseChillon, Maria CarmenCarrillo-Cruz, EstrellaBilbao-Sieyro, CristinaPrados de la Torre, EstherMartinez-Cuadron, DavidRodriguez-Veiga, RebecaBoluda, BlancaGil, CristinaBernal, TeresaBergua, Juan MiguelAlgarra, LorenzoTormo, MarMartinez-Sanchez, PilarSoria, ElenaSerrano, JosefinaAlonso-Dominguez, Juan ManuelGarcia-Boyero, RaimundoAmigo, Maria LuzHerrera-Puente, PilarSayas, Maria JoseLavilla-Rubira, EsperanzaMartinez-Lopez, JoaquinCalasanz, Maria JoseGarcia-Sanz, RamonPerez-Simon, Jose AntonioGomez-Casares, Maria TeresaSanchez-Garcia, JoaquinBarragan, EvaMontesinos, PauOn Behalf Of Pethema Groupacute myeloid leukemiaNext-Generation Sequencingcross-validationsmutational profilegenomic classificationclinical validationSimple Summary Next-Generation Sequencing (NGS) has provided a deeper genetic understanding of acute myeloid leukemia (AML) that has been recently incorporated into AML classification and risk-stratification guidelines. Single molecular analysis has become inefficient and molecular testing based on NGS is emerging as an irreplaceable diagnostic tool in clinical settings. The PETHEMA cooperative group has constituted a nationwide NGS network with centralized analysis in seven high-skilled laboratories. The study of molecular profiles in the "real-life" PETHEMA cohort supports the increasing role of NGS on the clinical management of AML patients. 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.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/17130CancersISSN: 20726694reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p171302026-06-07T16:35:31Z |
| 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, Claudia acute myeloid leukemia Next-Generation Sequencing cross-validations mutational profile genomic classification clinical validation |
| 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, Claudia Ayala, Rosa Larrayoz, Maria Jose Chillon, Maria Carmen Carrillo-Cruz, Estrella Bilbao-Sieyro, Cristina Prados de la Torre, Esther Martinez-Cuadron, David Rodriguez-Veiga, Rebeca Boluda, Blanca Gil, Cristina Bernal, Teresa Bergua, Juan Miguel Algarra, Lorenzo Tormo, Mar Martinez-Sanchez, Pilar Soria, Elena Serrano, Josefina Alonso-Dominguez, Juan Manuel Garcia-Boyero, Raimundo Amigo, Maria Luz Herrera-Puente, Pilar Sayas, Maria Jose Lavilla-Rubira, Esperanza Martinez-Lopez, Joaquin Calasanz, Maria Jose Garcia-Sanz, Ramon Perez-Simon, Jose Antonio Gomez-Casares, Maria Teresa Sanchez-Garcia, Joaquin Barragan, Eva Montesinos, Pau On Behalf Of Pethema Group |
| author |
Sargas, Claudia |
| author_facet |
Sargas, Claudia Ayala, Rosa Larrayoz, Maria Jose Chillon, Maria Carmen Carrillo-Cruz, Estrella Bilbao-Sieyro, Cristina Prados de la Torre, Esther Martinez-Cuadron, David Rodriguez-Veiga, Rebeca Boluda, Blanca Gil, Cristina Bernal, Teresa Bergua, Juan Miguel Algarra, Lorenzo Tormo, Mar Martinez-Sanchez, Pilar Soria, Elena Serrano, Josefina Alonso-Dominguez, Juan Manuel Garcia-Boyero, Raimundo Amigo, Maria Luz Herrera-Puente, Pilar Sayas, Maria Jose Lavilla-Rubira, Esperanza Martinez-Lopez, Joaquin Calasanz, Maria Jose Garcia-Sanz, Ramon Perez-Simon, Jose Antonio Gomez-Casares, Maria Teresa Sanchez-Garcia, Joaquin Barragan, Eva Montesinos, Pau On Behalf Of Pethema Group |
| author_role |
author |
| author2 |
Ayala, Rosa Larrayoz, Maria Jose Chillon, Maria Carmen Carrillo-Cruz, Estrella Bilbao-Sieyro, Cristina Prados de la Torre, Esther Martinez-Cuadron, David Rodriguez-Veiga, Rebeca Boluda, Blanca Gil, Cristina Bernal, Teresa Bergua, Juan Miguel Algarra, Lorenzo Tormo, Mar Martinez-Sanchez, Pilar Soria, Elena Serrano, Josefina Alonso-Dominguez, Juan Manuel Garcia-Boyero, Raimundo Amigo, Maria Luz Herrera-Puente, Pilar Sayas, Maria Jose Lavilla-Rubira, Esperanza Martinez-Lopez, Joaquin Calasanz, Maria Jose Garcia-Sanz, Ramon Perez-Simon, Jose Antonio Gomez-Casares, Maria Teresa Sanchez-Garcia, Joaquin Barragan, Eva Montesinos, Pau On Behalf Of Pethema Group |
| 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 author |
| dc.subject.none.fl_str_mv |
acute myeloid leukemia Next-Generation Sequencing cross-validations mutational profile genomic classification clinical validation |
| topic |
acute myeloid leukemia Next-Generation Sequencing cross-validations mutational profile genomic classification clinical validation |
| description |
Simple Summary Next-Generation Sequencing (NGS) has provided a deeper genetic understanding of acute myeloid leukemia (AML) that has been recently incorporated into AML classification and risk-stratification guidelines. Single molecular analysis has become inefficient and molecular testing based on NGS is emerging as an irreplaceable diagnostic tool in clinical settings. The PETHEMA cooperative group has constituted a nationwide NGS network with centralized analysis in seven high-skilled laboratories. The study of molecular profiles in the "real-life" PETHEMA cohort supports the increasing role of NGS on the clinical management of AML patients. 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://incliva.portalinvestigacion.com/publicaciones/17130 |
| url |
https://incliva.portalinvestigacion.com/publicaciones/17130 |
| 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-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname:INCLIVA |
| instname_str |
INCLIVA |
| reponame_str |
r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| collection |
r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869418352276930560 |
| score |
15,812429 |