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. SOURCE: Hamza CELIK (hcelik@wustl.edu) - Challen Lab Washington University in St Louis

Pluto Bioinformatics

GSE120595: Jarid2 Functions as a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells