JARID2 Functions As a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 Nov 14

PMID 30423295

Citations 31

Authors

Hamza Celik

Won Kyun Koh

Ashley C Kramer

Elizabeth L Ostrander

Cates Mallaney

Daniel A C Fisher

Jingyu Xiang

William C Wilson

Andrew Martens

Alok Kothari

Gregory Fishberger

Eric Tycksen

Darja Karpova

Eric J Duncavage

Youngsook Lee

Stephen T Oh

Grant A Challen

Affiliations

Soon will be listed here.

Abstract

How specific genetic lesions contribute to transformation of non-malignant myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs) to secondary acute myeloid leukemia (sAML) are poorly understood. JARID2 is lost by chromosomal deletions in a proportion of MPN/MDS cases that progress to sAML. In this study, genetic mouse models and patient-derived xenografts demonstrated that JARID2 acts as a tumor suppressor in chronic myeloid disorders. Genetic deletion of Jarid2 either reduced overall survival of animals with MPNs 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 potential therapeutic targets.

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