PS982 THE ROLE OF STAT3 ISOFORMS IN ACUTE MYELOID LEUKEMIA
Bibliographic record
Abstract
Background: Signal transducer and activator of transcription 3 (STAT3) plays a central role in proliferation, differentiation and oncogenic transformation. It is expressed in two alternatively spliced isoforms, STAT3α and truncated STAT3β, which lacks the C‐terminal transactivation domain and instead carries seven unique amino acids. Interestingly, STAT3β recently gained attention as a powerful anti‐tumorigenic molecule and protective prognostic marker. This has been shown in patients with esophageal squamous cell carcinoma as well as in mouse models for breast, skin and colon cancer. Deregulated STAT3 signaling is frequently observed in leukemogenesis and generally associated with a poor clinical outcome in patients with acute myeloid leukemia (AML). In addition, it has been shown that the expression ratios of STAT3α and STAT3β change upon myeloid differentiation. However, the exact role of STAT3β in AML patients and during disease progression remains unknown. Aims: The goal of our study is to analyze the contribution of the two STAT3 isoforms to leukemogenesis with a particular focus on STAT3β in AML development. Methods: We analyzed more than 50 AML patient samples for STAT3β/STAT3α mRNA expression levels and its correlation with clinical prognosis and overall survival. Furthermore, we generated an inducible Stat3β transgenic mouse model and crossed it with Pten ‐deficient mice, a previously described model for AML. In addition, we used fetal liver‐derived stem cells from Stat3β transgenic mice, transduced with a retrovirus encoding for the MLL‐AF9 translocation, in a transplant model for AML. Results: We observed a correlation between clinical prognosis and STAT3β/STAT3α expression ratio. A higher STAT3β/STAT3α ratio was further associated with a favorable clinical prognosis and a significantly increased overall survival. In both in vivo mouse models we could demonstrate that the expression of STAT3β impairs leukemogenesis and leukemic cell infiltration into hematopoietic organs. The STAT3β‐dependent delay in disease progression and leukemic infiltration resulted in a significant increase of overall survival. Summary/Conclusion: In summary, the results of our study demonstrate STAT3β as an anti‐tumorigenic molecule in AML mouse models and the STAT3β/STAT3α ratio in AML patient derived blasts positively correlates with survival.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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; both teacher heads agree on what is shown here.
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".