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Record W3043435386 · doi:10.1038/s41467-020-17064-0

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

2020· article· en· W3043435386 on OpenAlexafffund
Slim Mzoughi, Jia Yi Fong, David Papadopoli, Cheryl M. Koh, Laura Hulea, Paolo Pigini, Federico Di Tullio, Giuseppe Andreacchio, Michał 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 Teo, Cheng 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 D. Jeyasekharan, David Dominguez-Sola, Ivan Topisirović, Ernesto Guccione

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Hypoxia, and Metabolism
Canadian institutionsUniversité de MontréalHôpital Maisonneuve-RosemontMcGill University
FundersNational Cancer InstituteBiomedical Research CouncilNational Medical Research CouncilFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchTerry Fox FoundationNational Institutes of HealthMedical Research CouncilTerry Fox Research InstituteAgency for Science, Technology and ResearchInstitute of Molecular and Cell BiologyDeutsches KrebsforschungszentrumCenter for Strategic Scientific Initiatives, National Cancer InstituteMcGill UniversityTanoto FoundationIcahn School of Medicine at Mount Sinai
KeywordsRegulatorKey (lock)Cell metabolismComputational biologyCell biologyBiologyCellGeneticsGeneEcology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.294
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations49
Published2020
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicCancer, Hypoxia, and MetabolismFrench-language works237,207