TY - JOUR
T1 - PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis
AU - Mzoughi, Slim
AU - Fong, Jia Yi
AU - Papadopoli, David
AU - Koh, Cheryl M.
AU - Hulea, Laura
AU - Pigini, Paolo
AU - Di Tullio, Federico
AU - Andreacchio, Giuseppe
AU - Hoppe, Michal Marek
AU - Wollmann, Heike
AU - Low, Diana
AU - Caldez, Matias J.
AU - Peng, Yanfen
AU - Torre, Denis
AU - Zhao, Julia N.
AU - Uchenunu, Oro
AU - Varano, Gabriele
AU - Motofeanu, Corina Mihaela
AU - Lakshmanan, Manikandan
AU - Teo, Shun Xie
AU - Wun, Cheng Mun
AU - Perini, Giovanni
AU - Tan, Soo Yong
AU - Ong, Chee Bing
AU - Al-Haddawi, Muthafar
AU - Rajarethinam, Ravisankar
AU - Hue, Susan Swee Shan
AU - Lim, Soon Thye
AU - Ong, Choon Kiat
AU - Huang, Dachuan
AU - Ng, Siok Bian
AU - Bernstein, Emily
AU - Hasson, Dan
AU - Wee, Keng Boon
AU - Kaldis, Philipp
AU - Jeyasekharan, Anand
AU - Dominguez-sola, David
AU - Topisirovic, Ivan
AU - Guccione, Ernesto
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85087990243&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17064-0
DO - 10.1038/s41467-020-17064-0
M3 - Article
C2 - 32665551
AN - SCOPUS:85087990243
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3520
ER -
