Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells
Bibliographic record
Abstract
Venetoclax (VCX) is a BCL2 inhibitor approved for treating B cell-derived leukemia, including chronic lymphocytic leukemia (CLL). VCX’s role in apoptosis induction is well-defined, whereas its other mechanistic roles need to be clarified. Autophagy is an intracellular degradation process involving the lysosome, playing a fundamental role in cancer cell survival and death. In this study, we aim to investigate VCX’s function in autophagy. Following the measurement of autophagic flux by western blot and fluorescent microscopy, we demonstrate that VCX is a novel autophagy inhibitor and reduces the level of the essential autophagy pathway protein ATG12 (autophagy-related 12). VCX sensitizes B cell lines and primary CLL cells to cell death induced by amino acid starvation or ibrutinib. These findings provide a rationale for VCX treatment in combination therapies that inhibit the pro-cell survival function of autophagy in B cell-derived malignancies.Abbreviations: ATG12, autophagy-related 12; BCL2, BCL2 apoptosis regulator; CLL, chronic lymphocytic leukemia; CQ, chloroquine; IBR, ibrutinib; BTK, Bruton’s tyrosine kinase; LC3B, MAP1LC3B (microtubule-associated protein 1 light chain 3 beta); VCX, venetoclax; BECN1, beclin 1
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 0.001 |
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".