<i>HOX-PBX</i>Up-regulation Predicts Favorable Prognosis in NPM1-mutated Normal Cytogenetic AML<i>via</i>WNT Signaling
Why this work is in the frame
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Bibliographic record
Abstract
<h3>Background/Aim:</h3> Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy. <i>HOX</i> gene dysregulation, particularly within the <i>HOXA</i> cluster, plays a critical role in leukemogenesis. This study investigated the impact of <i>HOX-PBX</i> gene expression and its association with clinical outcomes in <i>NPM1</i>-mutated cytogenetically normal (CN)-AML. <h3>Materials and Methods:</h3> Gene expression analysis was performed on diagnostic bone marrow samples from 35 CN-AML patients using the NanoString nCounter platform. Differential expression of <i>HOXA9, HOXA10</i>, and <i>PBX3</i> was assessed, along with correlations with <i>NPM1</i> mutation status and WNT pathway activation. Kaplan–Meier survival analysis was conducted to evaluate prognostic significance. <h3>Results:</h3> <i>HOXA9</i> and <i>HOXA10</i> were significantly up-regulated in <i>NPM1</i>-mutated AML compared to NPM1-negative cases (<i>p</i><0.001). <i>PBX3</i> expression strongly correlated with <i>HOXA10</i> (r=0.86, <i>p</i><0.001), suggesting a cooperative role in leukemogenesis. Elevated <i>HOXA9</i> (>589.7) was associated with improved survival (hazard ratio=0.3, <i>p</i>=0.021). Up-regulated WNT pathway targets (<i>MYC, RUNX1</i>) in NPM1-mutated cases indicate active WNT/β-catenin signaling, potentially promoting differentiation and favorable prognosis. <h3>Conclusion:</h3> <i>HOX-PBX-WNT</i> interactions contribute to the distinct biology of <i>NPM1</i>-mutated CN-AML. Targeting this axis may offer novel therapeutic strategies for AML, warranting further research into molecular-driven treatments for 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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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