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

Author

Listed:
  • Slim Mzoughi

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore
    Icahn School of Medicine at Mount Sinai)

  • Jia Yi Fong

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore)

  • David Papadopoli

    (McGill University)

  • Cheryl M. Koh

    (Agency for Science, Technology and Research (A*STAR))

  • Laura Hulea

    (McGill University
    Maisonneuve-Rosemont Hospital Research Centre
    Université de Montréal)

  • Paolo Pigini

    (Agency for Science, Technology and Research (A*STAR)
    University of Bologna)

  • Federico Tullio

    (Agency for Science, Technology and Research (A*STAR))

  • Giuseppe Andreacchio

    (Agency for Science, Technology and Research (A*STAR)
    University of Bologna)

  • Michal Marek Hoppe

    (National University of Singapore)

  • Heike Wollmann

    (Agency for Science, Technology and Research (A*STAR))

  • Diana Low

    (Agency for Science, Technology and Research (A*STAR))

  • Matias J. Caldez

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore
    Immunology Frontiers Research Center, Osaka University)

  • Yanfen Peng

    (National University of Singapore)

  • Denis Torre

    (Icahn School of Medicine at Mount Sinai)

  • Julia N. Zhao

    (Icahn School of Medicine at Mount Sinai)

  • Oro Uchenunu

    (McGill University)

  • Gabriele Varano

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Corina-Mihaela Motofeanu

    (Agency for Science, Technology and Research (A*STAR))

  • Manikandan Lakshmanan

    (Agency for Science, Technology and Research (A*STAR))

  • Shun Xie Teo

    (Agency for Science, Technology and Research (A*STAR))

  • Cheng Mun Wun

    (Agency for Science, Technology and Research (A*STAR))

  • Giovanni Perini

    (University of Bologna)

  • Soo Yong Tan

    (Agency for Science, Technology and Research (A*STAR)
    IMCB
    National University of Singapore)

  • Chee Bing Ong

    (Agency for Science, Technology and Research (A*STAR)
    IMCB)

  • Muthafar Al-Haddawi

    (Agency for Science, Technology and Research (A*STAR)
    IMCB)

  • Ravisankar Rajarethinam

    (Agency for Science, Technology and Research (A*STAR)
    IMCB)

  • Susan Swee-Shan Hue

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore
    National University Hospital (NUH))

  • Soon Thye Lim

    (National Cancer Centre Singapore
    Duke-NUS Graduate Medical School)

  • Choon Kiat Ong

    (Duke-NUS Graduate Medical School
    National Cancer Centre Singapore
    Agency for Science, Technology and Research (A*STAR))

  • Dachuan Huang

    (National Cancer Centre Singapore)

  • Siok-Bian Ng

    (National University of Singapore
    National University of Singapore)

  • Emily Bernstein

    (Icahn School of Medicine at Mount Sinai)

  • Dan Hasson

    (Icahn School of Medicine at Mount Sinai)

  • Keng Boon Wee

    (Agency for Science, Technology and Research (A*STAR))

  • Philipp Kaldis

    (Agency for Science, Technology and Research (A*STAR))

  • Anand Jeyasekharan

    (National University of Singapore)

  • David Dominguez-sola

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Ivan Topisirovic

    (McGill University
    McGill University)

  • Ernesto Guccione

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

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.

Suggested Citation

  • Slim Mzoughi & Jia Yi Fong & David Papadopoli & Cheryl M. Koh & Laura Hulea & Paolo Pigini & Federico Tullio & Giuseppe Andreacchio & Michal Marek Hoppe & Heike Wollmann & Diana Low & Matias J. Caldez, 2020. "PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17064-0
    DOI: 10.1038/s41467-020-17064-0
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    Cited by:

    1. Qing Li & Liren Zhang & Wenhua You & Jiali Xu & Jingjing Dai & Dongxu Hua & Ruizhi Zhang & Feifan Yao & Suiqing Zhou & Wei Huang & Yongjiu Dai & Yu Zhang & Tasiken Baheti & Xiaofeng Qian & Liyong Pu &, 2022. "PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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