PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis

Slim Mzoughi, Jia Yi Fong, David Papadopoli, Cheryl M. Koh, Laura Hulea, Paolo Pigini, Federico Di Tullio, Giuseppe Andreacchio, Michal Marek Hoppe, Heike Wollmann, Diana Low, Matias J. Caldez, Yanfen Peng, Denis Torre, Julia N. Zhao, Oro Uchenunu, Gabriele Varano, Corina Mihaela Motofeanu, Manikandan Lakshmanan, Shun Xie TeoCheng Mun Wun, Giovanni Perini, Soo Yong Tan, Chee Bing Ong, Muthafar Al-Haddawi, Ravisankar Rajarethinam, Susan Swee Shan Hue, Soon Thye Lim, Choon Kiat Ong, Dachuan Huang, Siok Bian Ng, Emily Bernstein, Dan Hasson, Keng Boon Wee, Philipp Kaldis, Anand Jeyasekharan, David Dominguez-sola, Ivan Topisirovic, Ernesto Guccione

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish
Article number3520
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 1 Dec 2020

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