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Jarid2 Functions as a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells

ABSTRACT: How specific genetic lesions contribute to transformation of non-malignant myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) are poorly understood. The JARID2 gene is lost by chromosomal deletions in a proportion of MPN/MDS patients who progress to sAML. In this study, genetic mouse models and patient-derived xenografts (PDX) demonstrated that Jarid2 acts as a tumor suppressor in chronic myeloid disorders. Genetic deletion of Jarid2 either reduced overall survival of MPN, or drove transformation to sAML, depending on the timing and context of co-operating mutations. Mechanistically, Jarid2 recruits PRC2 to epigenetically repress self-renewal pathways in hematopoietic progenitor cells. These studies establish Jarid2 as a bona fide hematopoietic tumor suppressor and highlight new therapeutic targets.

ORGANISM(S): Mus musculus

PROVIDER: GSE120595 | GEO | 2018/09/30

REPOSITORIES: GEO

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