Investigating the Role of 3-ketosphinganine Reductase (KDSR) in Acute Myeloid Leukemia
Bibliographic record
Abstract
AML is characterized by accumulation of poorly differentiated, non-functional myeloblasts in the bone marrow and blood. Despite therapeutic advancements, AML remains a disease with poor long-term survival rates. To develop improved therapeutic strategies, this study aims to understand and target sphingolipid metabolism in AML. Sphingolipids are a heterogenous class of lipids that share an 18-carbon amino alcohol backbone. Bioactive sphingolipids regulate leukemic cell survival, apoptosis, chemoresistance, and differentiation. In this study, we show that early sphingolipid synthesis enzyme, 3-ketosphinganine reductase (KDSR), is essential for AML pathogenesis. KDSR is overexpressed in primary AML patient samples compared to healthy controls. Knockdown of KDSR impairs proliferation, viability, and self-renewal properties in AML cell lines. Using liquid-chromatography mass-spectrometry, we show that lack of KDSR activity induces a significant change in the cellular lipidome. Altogether, our findings suggest that KDSR promotes AML pathogenesis by regulating lipid homeostasis, thereby proposing KDSR as a novel target in 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) | 0.001 | 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".