Faculty Opinions recommendation of PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis.
Bibliographic record
Abstract
Primary refractory acute myeloid leukemia (AML) and early recurrence of leukemic cells are among the most difficult hurdles to overcome in the treatment of AML. Moreover, uncertainties surrounding the molecular mechanism underlying refractory AML pose a challenge when it comes to developing novel therapeutic drugs. However, accumulating evidence suggests a contribution of phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling to the development of refractory AML. To assess PTEN/AKT signaling in AML, two types of AML cell lines were evaluated, namely control HL60 cells and KG1α cells, a refractory AML cell line that is resistant to idarubicin and cytarabine (AraC) treatment. Changes in the expression level of glycolysis‑ and mitochondrial oxidative phosphorylation‑related genes and proteins were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The mitochondrial oxygen consumption and extracellular acidification rates were measured using an XF24 analyzer. CCK8 assay and Annexin V/PI staining were used to analyze cell viability and cellular apoptosis, respectively. The PTEN protein was found to be depleted, whereas AKT phosphorylation levels were elevated in KG1α cells compared with HL60 cells. These changes were associated with increased expression of glucose transporter 1 and hexokinase 2, and increased lactate production. AKT inhibition decreased the proliferation of KG1α cells and decreased extracellular acidification without affecting HL60 cells. Notably, AKT inhibition increased the susceptibility of KG1α cells to chemotherapy with idarubicin and AraC. Taken together, the findings of the present study indicate that activation of AKT by PTEN deficiency sustains the refractory AML status through enhancement of glycolysis and mitochondrial respiration, effects that may be rescued by inhibiting AKT activity. PMID: 31545464
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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 | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.006 | 0.003 |
| Insufficient payload (model declined to judge) | 0.345 | 0.158 |
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".