The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined f...

Descripción completa

Detalles Bibliográficos
Autores: Medina-Herrera, A, Vazquez, I, Cuenca, Isabel, Rosa-Rosa, J M, Ariceta, B, Jimenez, C, Fernandez-Mercado, M, Larrayoz, M J, Gutierrez, N C, Fernandez-Guijarro, M, Gonzalez-Calle, V, Rodriguez-Otero, Paula, Oriol, A, Rosiñol, Laura, Alegre, A, Escalante, Fernando, de la Rubia, Javier, Teruel, A I, de Arriba, Felipe, Hernández, Miguel-Teodoro, Lopez-Jimenez, J, Ocio, E M, Puig, N, Paiva, Bruno, Lahuerta, J J, Bladé, Joan, San Miguel, Jesus F., Mateos, Maria-Victoria, Martinez-Lopez, J, Calasanz, María-José, Garcia-Sanz, Ramon
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/20746
Acceso en línea:https://hdl.handle.net/20.500.13003/20746
Access Level:acceso abierto
Palabra clave:Disease Progression
Male
Aged
Mutation
Biomarkers, Tumor
Female
High-Throughput Nucleotide Sequencing
Drug Resistance, Neoplasm
Humans
Antineoplastic Combined Chemotherapy Protocols
Smoldering Multiple Myeloma
Middle Aged
Resistencia a Antineoplásicos
Mieloma Múltiple Quiescente
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Progresión de la Enfermedad
Femenino
Secuenciación de Nucleótidos de Alto Rendimiento
Biomarcadores de Tumor
Mutación
Masculino
id ES_4f441a8a786a130c1f3a7a333cdbb11a
oai_identifier_str oai:docusalut.com:20.500.13003/20746
network_acronym_str ES
network_name_str España
repository_id_str
spelling The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progressionMedina-Herrera, AVazquez, ICuenca, IsabelRosa-Rosa, J MAriceta, BJimenez, CFernandez-Mercado, MLarrayoz, M JGutierrez, N CFernandez-Guijarro, MGonzalez-Calle, VRodriguez-Otero, PaulaOriol, ARosiñol, LauraAlegre, AEscalante, Fernandode la Rubia, JavierTeruel, A Ide Arriba, FelipeHernández, Miguel-TeodoroLopez-Jimenez, JOcio, E MPuig, NPaiva, BrunoLahuerta, J JBladé, JoanSan Miguel, Jesus F.Mateos, Maria-VictoriaMartinez-Lopez, JCalasanz, María-JoséGarcia-Sanz, RamonDisease ProgressionMaleAgedMutationBiomarkers, TumorFemaleHigh-Throughput Nucleotide SequencingDrug Resistance, NeoplasmHumansAntineoplastic Combined Chemotherapy ProtocolsSmoldering Multiple MyelomaMiddle AgedResistencia a AntineoplásicosMieloma Múltiple QuiescenteHumanosPersona de Mediana EdadProtocolos de Quimioterapia Combinada AntineoplásicaAncianoProgresión de la EnfermedadFemeninoSecuenciación de Nucleótidos de Alto RendimientoBiomarcadores de TumorMutaciónMasculinoSmoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.Nature Portfolio20242024-04-2920242024-04-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/20746reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/207462026-06-22T12:44:07Z
dc.title.none.fl_str_mv The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
title The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
spellingShingle The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
Medina-Herrera, A
Disease Progression
Male
Aged
Mutation
Biomarkers, Tumor
Female
High-Throughput Nucleotide Sequencing
Drug Resistance, Neoplasm
Humans
Antineoplastic Combined Chemotherapy Protocols
Smoldering Multiple Myeloma
Middle Aged
Resistencia a Antineoplásicos
Mieloma Múltiple Quiescente
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Progresión de la Enfermedad
Femenino
Secuenciación de Nucleótidos de Alto Rendimiento
Biomarcadores de Tumor
Mutación
Masculino
title_short The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
title_full The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
title_fullStr The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
title_full_unstemmed The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
title_sort The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
dc.creator.none.fl_str_mv Medina-Herrera, A
Vazquez, I
Cuenca, Isabel
Rosa-Rosa, J M
Ariceta, B
Jimenez, C
Fernandez-Mercado, M
Larrayoz, M J
Gutierrez, N C
Fernandez-Guijarro, M
Gonzalez-Calle, V
Rodriguez-Otero, Paula
Oriol, A
Rosiñol, Laura
Alegre, A
Escalante, Fernando
de la Rubia, Javier
Teruel, A I
de Arriba, Felipe
Hernández, Miguel-Teodoro
Lopez-Jimenez, J
Ocio, E M
Puig, N
Paiva, Bruno
Lahuerta, J J
Bladé, Joan
San Miguel, Jesus F.
Mateos, Maria-Victoria
Martinez-Lopez, J
Calasanz, María-José
Garcia-Sanz, Ramon
author Medina-Herrera, A
author_facet Medina-Herrera, A
Vazquez, I
Cuenca, Isabel
Rosa-Rosa, J M
Ariceta, B
Jimenez, C
Fernandez-Mercado, M
Larrayoz, M J
Gutierrez, N C
Fernandez-Guijarro, M
Gonzalez-Calle, V
Rodriguez-Otero, Paula
Oriol, A
Rosiñol, Laura
Alegre, A
Escalante, Fernando
de la Rubia, Javier
Teruel, A I
de Arriba, Felipe
Hernández, Miguel-Teodoro
Lopez-Jimenez, J
Ocio, E M
Puig, N
Paiva, Bruno
Lahuerta, J J
Bladé, Joan
San Miguel, Jesus F.
Mateos, Maria-Victoria
Martinez-Lopez, J
Calasanz, María-José
Garcia-Sanz, Ramon
author_role author
author2 Vazquez, I
Cuenca, Isabel
Rosa-Rosa, J M
Ariceta, B
Jimenez, C
Fernandez-Mercado, M
Larrayoz, M J
Gutierrez, N C
Fernandez-Guijarro, M
Gonzalez-Calle, V
Rodriguez-Otero, Paula
Oriol, A
Rosiñol, Laura
Alegre, A
Escalante, Fernando
de la Rubia, Javier
Teruel, A I
de Arriba, Felipe
Hernández, Miguel-Teodoro
Lopez-Jimenez, J
Ocio, E M
Puig, N
Paiva, Bruno
Lahuerta, J J
Bladé, Joan
San Miguel, Jesus F.
Mateos, Maria-Victoria
Martinez-Lopez, J
Calasanz, María-José
Garcia-Sanz, Ramon
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
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Disease Progression
Male
Aged
Mutation
Biomarkers, Tumor
Female
High-Throughput Nucleotide Sequencing
Drug Resistance, Neoplasm
Humans
Antineoplastic Combined Chemotherapy Protocols
Smoldering Multiple Myeloma
Middle Aged
Resistencia a Antineoplásicos
Mieloma Múltiple Quiescente
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Progresión de la Enfermedad
Femenino
Secuenciación de Nucleótidos de Alto Rendimiento
Biomarcadores de Tumor
Mutación
Masculino
topic Disease Progression
Male
Aged
Mutation
Biomarkers, Tumor
Female
High-Throughput Nucleotide Sequencing
Drug Resistance, Neoplasm
Humans
Antineoplastic Combined Chemotherapy Protocols
Smoldering Multiple Myeloma
Middle Aged
Resistencia a Antineoplásicos
Mieloma Múltiple Quiescente
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Progresión de la Enfermedad
Femenino
Secuenciación de Nucleótidos de Alto Rendimiento
Biomarcadores de Tumor
Mutación
Masculino
description Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-04-29
2024
2024-04-29
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/20746
url https://hdl.handle.net/20.500.13003/20746
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Portfolio
publisher.none.fl_str_mv Nature Portfolio
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407808766607360
score 15,812429

Similares en LA Referencia