<i>HOX-PBX</i>Up-regulation Predicts Favorable Prognosis in NPM1-mutated Normal Cytogenetic AML<i>via</i>WNT Signaling
Bibliographic record
Abstract
Background/Aim: Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy. HOX gene dysregulation, particularly within the HOXA cluster, plays a critical role in leukemogenesis. This study investigated the impact of HOX-PBX gene expression and its association with clinical outcomes in NPM1-mutated cytogenetically normal (CN)-AML. Materials and Methods: Gene expression analysis was performed on diagnostic bone marrow samples from 35 CN-AML patients using the NanoString nCounter platform. Differential expression of HOXA9, HOXA10, and PBX3 was assessed, along with correlations with NPM1 mutation status and WNT pathway activation. Kaplan–Meier survival analysis was conducted to evaluate prognostic significance. Results: HOXA9 and HOXA10 were significantly up-regulated in NPM1-mutated AML compared to NPM1-negative cases (p<0.001). PBX3 expression strongly correlated with HOXA10 (r=0.86, p<0.001), suggesting a cooperative role in leukemogenesis. Elevated HOXA9 (>589.7) was associated with improved survival (hazard ratio=0.3, p=0.021). Up-regulated WNT pathway targets (MYC, RUNX1) in NPM1-mutated cases indicate active WNT/β-catenin signaling, potentially promoting differentiation and favorable prognosis. Conclusion: HOX-PBX-WNT interactions contribute to the distinct biology of NPM1-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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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) | 0.002 | 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".