2026-08-28T12:19:15Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1553532025-04-30T19:28:41Zcom_10366_3974com_10366_3947com_10366_3946com_10366_3823col_10366_3975

Casado García, Ana Isidro Hernández, Marta Oak, Ninad Mayado Colino, Andrea Mann-Ran, Christine Raboso Gallego, Javier Alemán-Arteaga, Silvia Buhles, Alexandra Sterker, Dario Sánchez, Elena G. Martínez-Cano, Jorge Blanco Muñez, Óscar Javier Orfao de Matos Correia e Vale, José Alberto Alonso López, Diego Rivas Sanz, Javier de las Riesco Riesco, Susana Prieto Matos, Pablo González-Murillo, África García Criado, Francisco Javier García Cenador, María Begoña Radimerski, Thomas Ramírez-Orellana, Manuel Cobaleda, César Yang, Jun J. Vicente Dueñas, Carolina Weiss, Andreas Nichols, Kim E. Sánchez García, Isidro 2024-02-05T17:51:40Z 2024-02-05T17:51:40Z 2022 Casado-García, A., Isidro-Hernández, M., Oak, N., Mayado, A., Mann-Ran, C., Raboso-Gallego, J., Alemán-Arteaga, S., Buhles, A., Sterker, D., Sánchez, E. G., Martínez-Cano, J., Blanco, O., Orfao, A., Alonso-López, D., De Las Rivas, J., Riesco, S., Prieto-Matos, P., González-Murillo, Á., García Criado, F. J., … Sánchez-García, I. (2022). Transient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice. Cancer Research, 82(6), 1098-1109. https://doi.org/10.1158/0008-5472.CAN-21-3386 0008-5472 http://hdl.handle.net/10366/155353 10.1158/0008-5472.CAN-21-3386 1538-7445 [EN]Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Predinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens. Here we show in Pax5(+/-) mice that transient, early-life administration of clinically relevant doses of ruxolitinib, a JAK1/2 inhibitor, significantly mitigates the risk of B-ALL following exposure to infection; 1 of 29 animals treated with ruxolitinib developed B-ALL versus 8 of 34 untreated mice. Ruxolitinib treatment preferentially targeted Pax5(+/-) versus wild-type B-cell progenitors and exerted unique effects on the Pax5(+/-) B-cell progenitor transcriptional program. These findings provide the first in vivo evidence for a potential strategy to prevent B-ALL development. Significance: JAK/STAT inhibition suppresses tumorigenesis in a B-ALL-susceptible mouse model, presenting a novel approach to prevent B-ALL onset. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/embargoedAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Acute lymphoblastic-leukemia Somatic point mutations Incb018424 phosphate Infection exposure Cancer Transient inhibition of the JAK/STAT pathway prevents B-ALL development in genetically predisposed mice info:eu-repo/semantics/article