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

Mzoughi, Slim ; Fong, Jia Yi ; Papadopoli, David ; Koh, Cheryl M. ; Hulea, Laura ; Pigini, Paolo ; Di Tullio, Federico ; Andreacchio, Giuseppe ; Hoppe, Michal Marek and Wollmann, Heike , et al. (2020) In Nature Communications 11(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
11
issue
1
article number
3520
publisher
Nature Publishing Group
external identifiers
  • pmid:32665551
  • scopus:85087990243
ISSN
2041-1723
DOI
10.1038/s41467-020-17064-0
language
English
LU publication?
no
id
8355cd39-4609-4b60-a4e9-f7f987cc5156
date added to LUP
2020-07-29 13:16:02
date last changed
2024-05-15 15:33:50
@article{8355cd39-4609-4b60-a4e9-f7f987cc5156,
  abstract     = {{<p>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.</p>}},
  author       = {{Mzoughi, Slim and Fong, Jia Yi and Papadopoli, David and Koh, Cheryl M. and Hulea, Laura and Pigini, Paolo and Di Tullio, Federico and Andreacchio, Giuseppe and Hoppe, Michal Marek and Wollmann, Heike and Low, Diana and Caldez, Matias J. and Peng, Yanfen and Torre, Denis and Zhao, Julia N. and Uchenunu, Oro and Varano, Gabriele and Motofeanu, Corina Mihaela and Lakshmanan, Manikandan and Teo, Shun Xie and Wun, Cheng Mun and Perini, Giovanni and Tan, Soo Yong and Ong, Chee Bing and Al-Haddawi, Muthafar and Rajarethinam, Ravisankar and Hue, Susan Swee Shan and Lim, Soon Thye and Ong, Choon Kiat and Huang, Dachuan and Ng, Siok Bian and Bernstein, Emily and Hasson, Dan and Wee, Keng Boon and Kaldis, Philipp and Jeyasekharan, Anand and Dominguez-sola, David and Topisirovic, Ivan and Guccione, Ernesto}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-17064-0}},
  doi          = {{10.1038/s41467-020-17064-0}},
  volume       = {{11}},
  year         = {{2020}},
}