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Transient JAK/STAT pathway inhibition prevents natural occurring B-ALL development in genetically predisposed Pax5+/- mice

ABSTRACT: We used microarrays to investigate gene expression changes in bone marrow B220+ cells from Pax5+/- and wild-type mice after ruxolitinib treatment during 2 weeks. Preventing development of B cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects in children, is a longstanding and unsolved challenge in medicine. In humans and mice, germline alterations in the Pax5 gene can lead to B-ALL. Preclinical studies have shown that this malignant transformation only occurs under an immune stress through the accumulation of secondary mutations in the JAK/STAT pathway. Here we describe that transient oral administration of ruxolitinib, a drug targeting the JAK/STAT pathway, can mitigate the risk of B-ALL in Pax5+/- mice. Although exposure to infection strongly potentiates leukemogenesis, the development of B-ALL was significantly impeded by transient in vivo treatment of Pax5+/- mice with ruxolitinib early in life (p-value=0.0332). These findings provided the first in vivo evidence for an effective preventive strategy for B-ALL development in genetically predisposed mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE179182 | GEO | 2021/07/02

REPOSITORIES: GEO

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Transient JAK/STAT pathway inhibition prevents natural occurring B-ALL development in genetically predisposed Pax5+/- mice

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