2026-04-27T01:59:16Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/89532024-10-31T11:57:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Rodríguez-Hernández, Guillermo
author
Opitz, Friederike V
author
Delgado, Pilar
author
Walter, Carolin
author
Alvarez-Prado, Angel Francisco
author
González-Herrero, Inés
author
Auer, Franziska
author
Fischer, Ute
author
Janssen, Stefan
author
Bartenhagen, Christoph
author
Raboso-Gallego, Javier
author
Casado-García, Ana
author
Orfao, Alberto
author
Blanco, Oscar
author
Alonso-López, Diego
author
Rivas, Javier De Las
author
Tena-Dávila, Sara González de
author
Müschen, Markus
author
Dugas, Martin
author
Criado, Francisco Javier García
author
Cenador, María Begoña García
author
Vicente-Dueñas, Carolina
author
Hauer, Julia
author
Ramiro, Almudena R
author
Sanchez-Garcia, Isidro
author
Borkhardt, Arndt
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
German Cancer Consortium (Alemania)
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Junta de Castilla y León (España)
2020-01-29T11:40:51Z
2020-01-29T11:40:51Z
2019-12-05
Nat Commun. 2019; 10(1):5563
2041-1723
http://hdl.handle.net/20.500.12105/8953
31804490
10.1038/s41467-019-13570-y
2041-1723
Nature communications
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.
eng
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
journal article
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
URL
https://repisalud.isciii.es/bitstreams/12f41389-6809-4c4a-b5c2-75531ab82311/download
File
MD5
f36336274b2fb4ebcfecf077bf4845f4
1354344
application/pdf
InfectiousStimuliPromoteMalignant _2019.pdf
URL
https://repisalud.isciii.es/bitstreams/03e54432-f3af-4b6d-b0c8-fdab8ac235ec/download
File
MD5
6a8d7740418d69b2ace074821dc111da
10045727
application/pdf
InfectiousStimuliPromoteMalignant _2019_MOESM1_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/30fc5ccf-9897-4490-a3a1-dd33a6d62550/download
File
MD5
88f77a251c999d38d91082404244c042
507227
application/pdf
InfectiousStimuliPromoteMalignant _2019_MOESM2_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/ed24fb48-433b-4d77-ab38-0445ccee714c/download
File
MD5
4304fb9be63deb2662003e3a7d6afba4
70384
application/pdf
InfectiousStimuliPromoteMalignant _2019_MOESM3_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/786dd683-fe4d-4e1e-95d4-7b5356e769fb/download
File
MD5
1b088225bfcb82de084bb49ce358d3c2
676475
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
InfectiousStimuliPromoteMalignant _2019_MOESM4_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/556199ad-b647-47fb-af2b-eb9eaabfcf1b/download
File
MD5
e6634de8156ad0a767df7930536b4b2d
106681
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
InfectiousStimuliPromoteMalignant _2019_MOESM5_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/946788de-626e-4f5c-94dd-92782799dc04/download
File
MD5
df007e1fdd0aa2a33140d7119bf79ba4
67814
text/plain
InfectiousStimuliPromoteMalignant _2019.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/66bf871e-fb47-442f-abdc-b470f86a7cba/download
File
MD5
eccaa88374b3e8ec7de4302a3a93577e
30194
text/plain
InfectiousStimuliPromoteMalignant _2019_MOESM1_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/b87c8337-a17d-47b9-a53c-0788c186234a/download
File
MD5
968a354d02264e3e6344115c2973abc2
63026
text/plain
InfectiousStimuliPromoteMalignant _2019_MOESM2_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/65a66f37-3c64-4356-84f8-f0ea51f28ae2/download
File
MD5
0bc0306b9dfa3b729012c22f769b2724
423
text/plain
InfectiousStimuliPromoteMalignant _2019_MOESM3_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/1d4718b5-04bf-4478-9c29-7d8c25c34cbd/download
File
MD5
1b275bc0d94182d2cd3d299a03368a0c
100001
text/plain
InfectiousStimuliPromoteMalignant _2019_MOESM4_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/8710e607-e452-4c9f-840e-ea0a5b391985/download
File
MD5
0f501cc6c9848b31c6fe4fa208fe600a
100001
text/plain
InfectiousStimuliPromoteMalignant _2019_MOESM5_ESM.xlsx.txt