biostudies-literatureCasado-Garcia AMCIU/AEI/FEDERMINECO/FEDERAyuda para Contratos predoctorales para la formación de doctoresFEDERFundación Científica de la Asociación Española contra el CáncerNCI NIH HHSAmerican Lebanese Syrian AssociatedFEDER MINECOMiguel Servet Grant1098-1109https://www.ebi.ac.uk/biostudies/studies/S-EPMC9359729biostudies-literatureUnknown82(6)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. Preclinical 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 Pax5Cancer researchTransient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice.PMC9359729R01 CA241452SAF2015-64420-RCPII19/00024PRE2019-088887CSI021-19UIC-017CSI067-18SAF2017-83061-RPRYCO211305SANCCSI144P20CSI001U16RTI2018-093314-B-I00CSI234P18AES 2017-2020R01CA2414529659122185-122185-4-21Alonso-Lopez DRaboso-Gallego JBlanco OAleman-Arteaga SGarcia Criado FJOrfao ARiesco SSanchez-Garcia IYang JJVicente-Duenas CNichols KEMayado AOak NRamirez-Orellana MMartinez-Cano JPrieto-Matos PMann-Ran CBuhles AGonzalez-Murillo ASterker DCasado-Garcia AWeiss AGarcia Cenador MBRadimerski TSanchez EGCobaleda CIsidro-Hernandez MDe Las Rivas JfalseTransient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice.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. Preclinical 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 Pax52022-01-01T00:00:00Z2022 Mar2026-05-28T03:45:24.595Z2025-04-06T00:52:45.007ZS-EPMC93597293513187110.1158/0008-5472.CAN-21-3386