Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and differential response to GLS1 and glucose metabolism inhibition
Bibliographic record
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of malignant B cells, and their accumulation in the blood stream and homing tissues. In the CLL context, the chromosomal aberrations del17p and del11q, spanning TP53 and ATM locus, respectively, are considered poor outcome predictors 1 , 2 . As well, CD38, ZAP70, and unmutated status of the IgVH locus represent bad prognosis markers 1 . Despite the outstanding clinical results yielded by ibrutinib (mainly used in relapsed or refractory settings), no complete remission is guaranteed due to the arising of resistance and relapse upon treatment discontinuation. The lack of tailored therapies upon ibrutinib failure represents a major challenge, particularly in del11q and del17p cases refractory to conventional therapies 3 . Recently, the analysis of metabolic reprogramming has uncovered tumor cell vulnerabilities, leading to the development of novel therapeutic approaches; such as the use of ritonavir (glucose uptake inhibitor) and metformin (OxPhos inhibitor) for multiple myeloma treatment 4 .
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".