ArticleInternational journal of molecular sciences2026
CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL), driven by the BCR-ABL1 fusion, remains highly aggressive, with poor prognosis despite tyrosine kinase inhibitor (TKI) therapy. Aberrant PI3K/Akt/mTOR pathway activation contributes to resistance, warranting identification of predictive kinase biomarkers. To identify and validate critical phospho-kinase markers within the PI3K/Akt/mTOR axis as candidate adaptive signaling nodes and exploratory prognostic markers in Ph+ B-ALL. Network pharmacology using STRING and Cytoscape mapped the protein-protein interactions, identifying high-centrality nodes. Functional enrichment analyses (GO/KEGG) were then performed via ShinyGO. Experimentally, phospho-kinase arrays profiled 39 kinase phosphorylation sites in Ph+ B-ALL cells (SUPB-15) treated with PI3K/Akt/mTOR inhibitors (Rapamycin, GDC-0941, GSK690693, Perifosine). Gene expression was validated by RT-qPCR in 100 Ph+ B-ALL patients and protein validation employed Western blot in 50 patient samples with 15 and five healthy controls, respectively. Network analysis identified CREB1 and GSK3 isoforms as central hub regulators. Phospho-kinase profiling revealed p-CREB (Ser133) phosphorylation upregulation following Perifosine, GDC-0941, and Rapamycin treatment, with no statistically significant change after GSK690693. p-GSK3α/β (Ser21/9) phosphorylation showed a statistically significant increase after Perifosine, with non-significant trends after GDC-0941, and a significant reduction following Rapamycin. Hierarchical clustering then divided proteins into four distinct clusters positioning CREB1 in cluster 3 and GSK3α/β in cluster 2 as candidate adaptive response markers based on their phosphorylation profiles. RT-qPCR demonstrated marked downregulation of GSK3α (approximately 71%), GSK3β (63%), and CREB1 (65%) transcripts in patients versus controls, with even greater suppression seen in cell lines. Conversely, Western blot revealed a significant 2.49 fold elevated p-CREB (Ser133) (
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.