Flow cytometry‐based assessment of mitoxantrone efflux from leukemic blasts varies with response to induction chemotherapy in acute myeloid leukemia
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Accurate prediction of chemotherapy drug resistance would aid treatment decisions in acute myeloid leukemia (AML). The aim of this study was to determine if mitoxantrone efflux from AML blasts would correlate with response to induction chemotherapy. METHODS: Flow cytometry was used to measure the median fluorescence intensity (MFI) for AML blasts incubated with mitoxantrone [an ATP-binding cassette (ABC) transporter substrate] with or without coincubation with cyclosporine A (a broad-spectrum inhibitor of ABC transporters) and a ratio (MFIR) between the inhibited and uninhibited MFI was calculated. RESULTS: Among 174 AML patient blast samples, the mean MFIR for complete remission (CR) patients was lower than that obtained for induction failure (IF) patients (mean MFIR ± SD 1.62 ± 0.53 for CR after one cycle of chemotherapy vs. 2.22 ± 1.29 for CR after two cycles and 2.59 ± 0.98 for IF, P < 0.001). Logistic regression analysis determined 2.45 as the MFIR threshold above which 29% of patients achieved CR vs. a CR rate of 84% when the MFIR was ≤ 2.45 (P < 0.0001). In AML patients with normal karyotype (n = 80), CR was obtained for 33% of patients with an MFIR > 2.45 vs. 89% of those with MFIR ≤ 2.45 (P < 0.0001). In patients > age 60 (n = 77), 30% vs. 87% of those with MFIR > vs. ≤ 2.45 achieved CR (P < 0.0001). CONCLUSIONS: This assay of ABC transporter function can potentially predict response to induction chemotherapy in AML.
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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 | 0.008 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.005 | 0.012 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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 it