2026-04-26T23:42:37Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc 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 author 2023-08-24 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. 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 Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice