A prospective biomarker analysis of alvocidib followed by cytarabine and mitoxantrone in MCL-1-dependent relapsed/refractory acute myeloid leukemia
Bibliographic record
Abstract
Overall outcomes are dismal in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Alvocidib is a multi-cyclin-dependent kinase (multi-CDK) inhibitor with potent activity against CDK9. CDK9 forms a complex with cyclin T1, positive transcription elongation factor b, which exists in a superenhancer complex to regulate the activity of RNA-polymerase II. By inhibiting CDK9, alvocidib leads to the suppression of RNA-polymerase II-mediated transcription of myeloid cell leukemia-1 (MCL-1), a pro-survival BCL-2 family member that inhibits the intrinsic pathway of apoptosis and promotes leukemia survival [ 1 ]. MCL-1 has a short half-life and is dependent on continuous transcription from RNA-polymerase II for activity [ 2 ]. There is a strong rationale to investigate targeted strategies of MCL-1 inhibition in diverse AML treatment settings.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| 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 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".