B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model

Autores
Hussain, Tabish; Bramble, Matthew D.; Liu, Bin; Abba, Martín Carlos; Chesi, Marta; Aldaz, C. Marcelo
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon Wwox deletion in Vk∗MYC mice. Wwox KO plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell-specific Wwox deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.
Fil: Hussain, Tabish. University of Texas; Estados Unidos
Fil: Bramble, Matthew D.. University of Texas; Estados Unidos
Fil: Liu, Bin. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Chesi, Marta. University of Texas; Estados Unidos
Fil: Aldaz, C. Marcelo. University of Texas; Estados Unidos
Materia
B CELLS
MYELOMA
WWOX
CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/289540
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/289540
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma modelHussain, TabishBramble, Matthew D.Liu, BinAbba, Martín CarlosChesi, MartaAldaz, C. MarceloB CELLSMYELOMAWWOXCANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon Wwox deletion in Vk∗MYC mice. Wwox KO plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell-specific Wwox deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.Fil: Hussain, Tabish. University of Texas; Estados UnidosFil: Bramble, Matthew D.. University of Texas; Estados UnidosFil: Liu, Bin. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Chesi, Marta. University of Texas; Estados UnidosFil: Aldaz, C. Marcelo. University of Texas; Estados UnidosElsevier2025-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/289540Hussain, Tabish; Bramble, Matthew D.; Liu, Bin; Abba, Martín Carlos; Chesi, Marta; et al.; B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model; Elsevier; Blood Neoplasia; 2; 4; 11-2025; 1-142950-3280CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2950328025000883info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bneo.2025.100153info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:37:11Zoai:ri.conicet.gov.ar:11336/289540instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:37:11.843CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
title B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
spellingShingle B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
Hussain, Tabish
B CELLS
MYELOMA
WWOX
CANCER
title_short B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
title_full B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
title_fullStr B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
title_full_unstemmed B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
title_sort B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model
dc.creator.none.fl_str_mv Hussain, Tabish
Bramble, Matthew D.
Liu, Bin
Abba, Martín Carlos
Chesi, Marta
Aldaz, C. Marcelo
author Hussain, Tabish
author_facet Hussain, Tabish
Bramble, Matthew D.
Liu, Bin
Abba, Martín Carlos
Chesi, Marta
Aldaz, C. Marcelo
author_role author
author2 Bramble, Matthew D.
Liu, Bin
Abba, Martín Carlos
Chesi, Marta
Aldaz, C. Marcelo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv B CELLS
MYELOMA
WWOX
CANCER
topic B CELLS
MYELOMA
WWOX
CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon Wwox deletion in Vk∗MYC mice. Wwox KO plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell-specific Wwox deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.
Fil: Hussain, Tabish. University of Texas; Estados Unidos
Fil: Bramble, Matthew D.. University of Texas; Estados Unidos
Fil: Liu, Bin. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Chesi, Marta. University of Texas; Estados Unidos
Fil: Aldaz, C. Marcelo. University of Texas; Estados Unidos
description Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon Wwox deletion in Vk∗MYC mice. Wwox KO plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell-specific Wwox deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.
publishDate 2025
dc.date.none.fl_str_mv 2025-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/289540
Hussain, Tabish; Bramble, Matthew D.; Liu, Bin; Abba, Martín Carlos; Chesi, Marta; et al.; B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model; Elsevier; Blood Neoplasia; 2; 4; 11-2025; 1-14
2950-3280
CONICET Digital
CONICET
url http://hdl.handle.net/11336/289540
identifier_str_mv Hussain, Tabish; Bramble, Matthew D.; Liu, Bin; Abba, Martín Carlos; Chesi, Marta; et al.; B-cell–specific Wwox deletion promotes plasmablastic tumor development and proinflammatory signatures in myeloma model; Elsevier; Blood Neoplasia; 2; 4; 11-2025; 1-14
2950-3280
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2950328025000883
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bneo.2025.100153
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.24418

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