PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis.
Slim MzoughiJia Yi FongDavid PapadopoliCheryl M KohLaura HuleaPaolo PiginiFederico Di TullioGiuseppe AndreacchioMichal Marek HoppeHeike WollmannDiana LowMatias J CaldezYanfen PengDenis TorreJulia N ZhaoOro UchenunuGabriele VaranoCorina-Mihaela MotofeanuManikandan LakshmananShun Xie TeoCheng Mun WunGiovanni PeriniSoo Yong TanChee Bing OngMuthafar Al-HaddawiRavisankar RajarethinamSusan Swee-Shan HueSoon Thye LimChoon-Kiat OngDachuan HuangSiok-Bian NgEmily BernsteinDan HassonKeng Boon WeePhilipp KaldisAnand D JeyasekharanDavid Dominguez-SolaIvan TopisirovicErnesto GuccionePublished in: Nature communications (2020)
PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology.