Mechanisms underlying the variability in response of Acute Myelogenous Leukemia cells to the immunotoxin AVE9633
Bibliographic record
Abstract
Acute myelogenous leukemia (AML) five year survival ranges between 20-30% despite the administration of the most intensive chemotherapy regimen, hence the need to develop new therapeutic strategies. Substantial inter-patient variation in sensitivity to AVE9633, a very promising anti-CD33 immunoconjugate, was observed. The goal of this project is to identify the mechanisms underlying resistance of AML cells to AVE9633. Using the AVE9633 sensitive AML cell line, HL60, and its resistant variant HL60/s, we found that both internalize the immunotoxin to a similar extent. The uncoupling of the antibody from the CD33 receptor is significantly lower in HL60/s. CD33 degradation was seen to be reduced in the resistant cell line while Suppressor Of Cytokine Signalling 3, SOCS3, playing a role in CD33 degradation, is only expressed in the sensitive cell line. In conclusion, antibody-receptor uncoupling and CD33 degradation defects were shown to be associated with resistance to AVE9633 in the HL60/s cell line. The identification of these mechanisms of resistance could provide means to screen-out patients most likely to benefit from treatment with AVE9633 and identify new approaches to treat patients refractory to current cancer treatments.
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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 | 0.000 |
| 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 | 0.000 | 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 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".