Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidenc...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/8953 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/8953 |
| Access Level: | acceso abierto |
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Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AIDRodríguez-Hernández, GuillermoOpitz, Friederike VDelgado, PilarWalter, CarolinAlvarez-Prado, Angel FranciscoGonzález-Herrero, InésAuer, FranziskaFischer, UteJanssen, StefanBartenhagen, ChristophRaboso-Gallego, JavierCasado-García, AnaOrfao, AlbertoBlanco, OscarAlonso-López, DiegoRivas, Javier De LasTena-Dávila, Sara González deMüschen, MarkusDugas, MartinCriado, Francisco Javier GarcíaCenador, María Begoña GarcíaVicente-Dueñas, CarolinaHauer, JuliaRamiro, Almudena RSanchez-Garcia, IsidroBorkhardt, ArndtThe prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development.SpringerUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Instituto de Salud Carlos IIIGerman Cancer Consortium (Alemania)Unión Europea. Comisión EuropeaUnión Europea. Comisión Europea. European Research Council (ERC)Ministerio de Ciencia, Innovación y Universidades (España)Fundación ProCNICDeutsche Forschungsgemeinschaft (Alemania)Junta de Castilla y León (España)20202020-01-2920192019-12-0520192019-12-05journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheethttp://hdl.handle.net/20.500.12105/8953reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SEV-2015-0505 Not availableEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 207844open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/89532026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| title |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| spellingShingle |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID Rodríguez-Hernández, Guillermo |
| title_short |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| title_full |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| title_fullStr |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| title_full_unstemmed |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| title_sort |
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| dc.creator.none.fl_str_mv |
Rodríguez-Hernández, Guillermo Opitz, Friederike V Delgado, Pilar Walter, Carolin Alvarez-Prado, Angel Francisco González-Herrero, Inés Auer, Franziska Fischer, Ute Janssen, Stefan Bartenhagen, Christoph Raboso-Gallego, Javier Casado-García, Ana Orfao, Alberto Blanco, Oscar Alonso-López, Diego Rivas, Javier De Las Tena-Dávila, Sara González de Müschen, Markus Dugas, Martin Criado, Francisco Javier García Cenador, María Begoña García Vicente-Dueñas, Carolina Hauer, Julia Ramiro, Almudena R Sanchez-Garcia, Isidro Borkhardt, Arndt |
| author |
Rodríguez-Hernández, Guillermo |
| author_facet |
Rodríguez-Hernández, Guillermo Opitz, Friederike V Delgado, Pilar Walter, Carolin Alvarez-Prado, Angel Francisco González-Herrero, Inés Auer, Franziska Fischer, Ute Janssen, Stefan Bartenhagen, Christoph Raboso-Gallego, Javier Casado-García, Ana Orfao, Alberto Blanco, Oscar Alonso-López, Diego Rivas, Javier De Las Tena-Dávila, Sara González de Müschen, Markus Dugas, Martin Criado, Francisco Javier García Cenador, María Begoña García Vicente-Dueñas, Carolina Hauer, Julia Ramiro, Almudena R Sanchez-Garcia, Isidro Borkhardt, Arndt |
| author_role |
author |
| author2 |
Opitz, Friederike V Delgado, Pilar Walter, Carolin Alvarez-Prado, Angel Francisco González-Herrero, Inés Auer, Franziska Fischer, Ute Janssen, Stefan Bartenhagen, Christoph Raboso-Gallego, Javier Casado-García, Ana Orfao, Alberto Blanco, Oscar Alonso-López, Diego Rivas, Javier De Las Tena-Dávila, Sara González de Müschen, Markus Dugas, Martin Criado, Francisco Javier García Cenador, María Begoña García Vicente-Dueñas, Carolina Hauer, Julia Ramiro, Almudena R Sanchez-Garcia, Isidro Borkhardt, Arndt |
| 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 |
| dc.contributor.none.fl_str_mv |
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) Instituto de Salud Carlos III German Cancer Consortium (Alemania) Unión Europea. Comisión Europea Unión Europea. Comisión Europea. European Research Council (ERC) Ministerio de Ciencia, Innovación y Universidades (España) Fundación ProCNIC Deutsche Forschungsgemeinschaft (Alemania) Junta de Castilla y León (España) |
| description |
The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-12-05 2019 2019-12-05 2020 2020-01-29 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/8953 |
| url |
http://hdl.handle.net/20.500.12105/8953 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
ES SEV-2015-0505 Not available European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 207844 |
| 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 |
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open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| dc.publisher.none.fl_str_mv |
Springer |
| publisher.none.fl_str_mv |
Springer |
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reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
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Instituto de Salud Carlos III (ISCIII) |
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Repisalud |
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Repisalud |
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1869423263490244608 |
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15,812455 |