MétaCan
Menu
Back to cohort
Record W4403098034 · doi:10.1038/s41467-024-52826-0

Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas

2024· article· en· W4403098034 on OpenAlexaff
Anja Fischer, Thomas Albert, Natalia Moreno, Marta Interlandi, Jana Mormann, Selina Glaser, Paurnima Patil, Flavia W. de Faria, Mathis Richter, Archana Verma, Sebastian T. Balbach, Rabea Wagener, Susanne Bens, Sonja Dahlum, Carolin Göbel, Daniel Münter, Clara Inserte, Monika Graf, Eva Kremer, Viktoria Melcher, Gioia Di Stefano, Raffaella Santi, Alexander Chan, Ahmet Doǧan, Jonathan W. Bush, Martin Hasselblatt, Sylvia Cheng, Signe Spetalen, Alexander Fosså, Wolfgang Hartmann, Heidi Herbrüggen, Stella Robert, Florian Oyen, Martin Dugas, Carolin Walter, Sarah Sandmann, Julian Varghese, Claudia Rössig, Ulrich Schüller, Alexandar Tzankov, Martin Bjerregård Pedersen, Francesco d’Amore, Karin Mellgren, Udo Kontny, Venkatesh Kancherla, Luis Veloza, Edoardo Missiaglia, Virginie Fataccioli, Philippe Gaulard, Birgit Burkhardt, Oliver Soehnlein, Wolfgang Hiddemann, Laurence de Leval, Reiner Siebert, Kornelius Kerl

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChromatin Remodeling and Cancer
Canadian institutionsUniversity of British ColumbiaB.C. Women's Hospital & Health CentreBC Children's Hospital
FundersDeutsche KinderkrebsstiftungDeutsche KrebshilfeNational Cancer InstituteBundesministerium für Bildung und ForschungDeutsche Forschungsgemeinschaft
KeywordsPeripheralSMARCB1Expression (computer science)BiologyCancer researchCell biologyComputational biologyMedicineGeneticsGene expressionComputer scienceGeneInternal medicine

Abstract

fetched live from OpenAlex

Abstract Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS SMARCB1- , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS SMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS Smarcb1- . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS SMARCB1- within the TME.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.036
Threshold uncertainty score0.237

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.024
GPT teacher head0.330
Teacher spread0.306 · 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 teacher head, 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

Citations3
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicChromatin Remodeling and CancerFrench-language works237,207