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Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma

2022· article· en· W4291173185 on OpenAlexaff
Findlay Bewicke‐Copley, Koorosh Korfi, Shamzah Araf, Brendan P. Hodkinson, Emil Kumar, Thomas Cummin, Margaret Ashton‐Key, Sharon Barrans, Suzan van Hoppe, Cathy Burton, Mohamed Elshiekh, Simon Rule, Nicola Crosbie, Andrew Clear, Maria Calaminici, Hendrik F.P. Runge, Robert K. Hills, David W. Scott, Lisa M. Rimsza, Geetha R. Menon, Chulin Sha, John R. Davies, A. Nagano, Andrew Davies, Daniel Painter, Alexandra Smith, John G. Gribben, Kikkeri N. Naresh, David R. Westhead, Jessica Okosun, Andrew J. Steele, Daniel J. Hodson, Sriram Balasubramanian, Peter Johnson, Jun Wang, Jude Fitzgibbon

Bibliographic record

VenueBlood Advances · 2022
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsSpinal Cord Injury BCUniversity of British Columbia
FundersBlood Cancer UKAcademy of Medical SciencesCancer Research UKBarts CharityEuropean Hematology Association
KeywordsDiffuse large B-cell lymphomaOncologyLymphomaInternal medicinePopulationMedicineIbrutinibClinical trialGerminal centerGene signatureBiologyImmunologyB cellGeneChronic lymphocytic leukemiaLeukemiaGene expressionGenetics

Abstract

fetched live from OpenAlex

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell-like (ABC) to germinal center B-cell-like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.219
Threshold uncertainty score0.520

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 head0.007
GPT teacher head0.234
Teacher spread0.226 · 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 designObservational
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

Citations2
Published2022
Admission routes1
Has abstractyes

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