<i>Bfl‐1</i> is a crucial pro‐survival nuclear factor‐κB target gene in Hodgkin/Reed‐Sternberg cells
Bibliographic record
Abstract
Hodgkin/Reed-Sternberg (H/RS) cells are believed to represent clonal progeny of Germinal Centre B cells that have escaped negative selection by evading apoptosis. Aberrant constitutive activity of the transcription factor NF-κB plays a key role in the pathogenesis of Hodgkin's Lymphoma (HL), conferring a survival advantage on H/RS cells. Bfl-1 is a pro-survival NF-κB target gene from the Bcl-2 family of apoptosis-regulating proteins. Here, we report that bfl-1 (also known as A1 or GRS) is frequently expressed in primary H/RS cells from HL tumor biopsies and that elevated bfl-1 expression is a feature of H/RS derived cell lines. We show that bfl-1 is an NF-κB target gene in this cell context and that this regulation is effected through a p65-binding DNA element located in its promoter. We demonstrate that ectopic Bfl-1 can rescue cultured H/RS cells from apoptosis induced by pharmacological inhibitors of NF-κB, and that knockdown of bfl-1 potentiates the pro-apoptotic effect of these agents. These findings are the first indication that Bfl-1 plays a crucial role in setting the elevated threshold of resistance of this malignant cell type to apoptosis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".