IDENTIFYING MUTATIONS ENRICHED IN RELAPSED‐REFRACTORY DLBCL TO DERIVE GENETIC FACTORS UNDERLYING TREATMENT RESISTANCE
Bibliographic record
Abstract
around 30 distinct clinicopathological PTCL entities in the current WHO classification.Follicular helper T cells (TFH) appear as the cell counterpart of a major proportion of PTCL worldwide, including angio-immunoblastic T-cell lymphoma and other nodal lymphomas with a TFH phenotype; the later disclose a rather homogeneous mutational landscape which recapitulates a multi-step oncogenic process associating epigenetic deregulation (TET2 +/-DNMT3Amutations, often at early stages), and second hit mutations affecting the T-cell receptor signaling pathway (RHOA,..).This oncogenic model has been confirmed in mouse models and opens the field for using emerging epigenetic-or signalingmodulating therapies.Among anaplastic large cell lymphoma (ALCL), those with ALK rearrangement constitute the best-delineated entity.ALK-negative ALCLs appear genetically heterogeneous with translocation-associated subsets (DUSP22, TP63,…) found in both systemic and cutaneous types.DUSP22-rearranged ALK-negative ALCL likely constitutes a unique category with a distinct signature and a good outcome.Except for DUSP22-rearranged ALCL, a constitutive activation of STAT3 is shared by ALK-positive and ALK-negative ALCLs, including the newly described usually indolent breast implantassociated ALCL.Lymphomas derived from cells of the innate immune system affect preferentially extranodal sites, which are continuously exposed to various antigens.Chronic immunosuppression and genetic background may also play a role.There is evidence of plasticity in terms of cellular derivation (NK, Tγδ,Tαβ) within a single entity.Most of these tumors also harbor a combination of mutations affecting different classes of epigenetic modifyers, and mutation-induced activation of the JAK-STAT pathway which may serve as potential therapeutic targets.While most of these proliferations are highly malignant, some more indolent forms have been identified, arising in the skin or the GI tract.Despite significant progress in the understanding of PTCLs, 20-30% of PTCL patients remain "unspecified", a basket category which may contain emerging (GATA3 or T-bet) subtypes.Most PTCL probably harbor distinct therapeutic vulnerabilities supporting the need for biologically-oriented therapeutic strategies to improve patient's outcome.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".