Deciphering the oncogenic network of PRC-2 loss guided leukemogenesis

Introduction: Mutations in EZH2 (including -7/-7q) and other PRC2 subunits have been described in adults with AML and MDS, in children with Down syndrome AML or JMML. Since myeloid neoplasms are elicited by accumulation of cooperating mutations, we aimed to decipher oncogenic cooperation with loss of PRC2-activity. Results: To this end, CRISPR-Cas9 screenings with oncogene/tumor suppressor pools (a total of 15 candidate genes) were performed in vitro and in vivo. In murine transplants this strategy highlighted Nf1, Dnmt3a and Runx1 as potential cooperating partners of Ezh2 loss during the induction of AML. Furth…