1. PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis
- Author
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Heike Wollmann, David Papadopoli, Ravisankar Rajarethinam, Giovanni Perini, Michal Marek Hoppe, Laura Hulea, Soo Yong Tan, Emily Bernstein, Susan Swee Shan Hue, Choon Kiat Ong, Siok Bian Ng, Soon Thye Lim, Slim Mzoughi, Cheryl M. Koh, Ivan Topisirovic, Federico Di Tullio, Manikandan Lakshmanan, Corina Mihaela Motofeanu, Ernesto Guccione, Cheng Mun Wun, Oro Uchenunu, Chee Bing Ong, David Dominguez-Sola, Shun Xie Teo, Diana Low, Giuseppe Andreacchio, Gabriele Varano, Dachuan Huang, Muthafar Al-Haddawi, Paolo Pigini, Denis Torre, Y Peng, Anand D. Jeyasekharan, Julia N. Zhao, Philipp Kaldis, Jia Yi Fong, Matias J. Caldez, Keng Boon Wee, Dan Hasson, Mzoughi, Slim, Fong, Jia Yi, Papadopoli, David, Koh, Cheryl M, Hulea, Laura, Pigini, Paolo, Di Tullio, Federico, Andreacchio, Giuseppe, Hoppe, Michal Marek, Wollmann, Heike, Low, Diana, Caldez, Matias J, Peng, Yanfen, Torre, Deni, Zhao, Julia N, Uchenunu, Oro, Varano, Gabriele, Motofeanu, Corina-Mihaela, Lakshmanan, Manikandan, Teo, Shun Xie, Wun, Cheng Mun, Perini, Giovanni, Tan, Soo Yong, Ong, Chee Bing, Al-Haddawi, Muthafar, Rajarethinam, Ravisankar, Hue, Susan Swee-Shan, Lim, Soon Thye, Ong, Choon Kiat, Huang, Dachuan, Ng, Siok-Bian, Bernstein, Emily, Hasson, Dan, Wee, Keng Boon, Kaldis, Philipp, Jeyasekharan, Anand, Dominguez-Sola, David, Topisirovic, Ivan, and Guccione, Ernesto
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0301 basic medicine ,Lymphoma ,Transcription Factor ,Somatic cell ,Regulator ,General Physics and Astronomy ,Apoptosis ,Mice, SCID ,Mice ,Phosphatidylinositol 3-Kinases ,Random Allocation ,0302 clinical medicine ,lcsh:Science ,Multidisciplinary ,B-cell lymphoma ,Flow Cytometry ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Human ,Chromatin Immunoprecipitation ,Cell Survival ,DNA-Binding Protein ,Science ,Blotting, Western ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,NO ,03 medical and health sciences ,medicine ,Animals ,Humans ,Transcriptomics ,Gene ,Protein kinase B ,PI3K/AKT/mTOR pathway ,B cell ,Animal ,Apoptosi ,Computational Biology ,General Chemistry ,medicine.disease ,030104 developmental biology ,Gene Expression Regulation ,lcsh:Q ,Phosphatidylinositol 3-Kinase ,Transcriptome ,Chromatin immunoprecipitation ,Transcription Factors - 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., The transcriptional regulator PRDM15 is expressed at low levels in normal tissues but overexpressed in B-cell lymphomas. Here, the authors show that PRDM15 depletion does not affect adult somatic cell homeostasis but leads to a metabolic crisis which impairs B-cell lymphomagenesis.
- Published
- 2020
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