2026-04-26T23:42:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/168392024-11-28T17:25:39Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16960
Repisalud
author
Isidro-Hernández, Marta
author
Casado-García, Ana
author
Oak, Ninad
author
Alemán-Arteaga, Silvia
author
Ruiz-Corzo, Belén
author
Martínez-Cano, Jorge
author
Mayado, Andrea
author
Sánchez, Elena G
author
Blanco, Oscar
author
Gaspar, Maria Luisa
author
Orfao, Alberto
author
Alonso-López, Diego
author
De Las Rivas, Javier
author
Riesco, Susana
author
Prieto-Matos, Pablo
author
González-Murillo, África
author
García-Criado, Francisco Javier
author
García-Cenador, María Begoña
author
Ramírez-Orellana, Manuel
author
Andres, Belen de
author
Vicente-Dueñas, Carolina
author
Cobaleda, César
author
Nichols, Kim E
author
Sánchez-García, Isidro
funder
Ministerio de Ciencia e Innovación (España)
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación Ramón Areces
funder
Banco Santander
funder
Instituto de Salud Carlos III
funder
American Lebanese Syrian Associated Charities
funder
Junta de Castilla y León (España)
funder
Fundación Unoentrecienmil
funder
Asociación Española Contra el Cáncer
funder
National Cancer Research Institute
2023-12-18T20:38:11Z
2023-12-18T20:38:11Z
2023-08-24
Nat Commun. 2023 Aug 24;14(1):5159.
http://hdl.handle.net/20.500.12105/16839
37620322
10.1038/s41467-023-40961-z
2041-1723
Nature communications
The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5+/- B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5+/-Myd88+/- mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5+/- mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.
eng
Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice
research article
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