ArticleLeukemia2014
Cytotoxic activity of the casein kinase 2 inhibitor CX-4945 against T-cell acute lymphoblastic leukemia: targeting the unfolded protein response signaling.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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
56 citing papers in PubMed, 81 citations in OpenAlex.
- CK2α Regulates Endoplasmic Reticulum Stress-Mediated Mitophagy via the PERK/ATF4/CHOP Pathway in Rotenone-Treated SH-SY5Y Cells.Molecular neurobiology · 2025Article
- The Roles of PTEN in Melanoma Suppression.Pigment cell & melanoma research · 2025Review
- Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL.Blood · 2025Article
- Characterization ofInternational journal of molecular sciences · 2025Article
- Protective effect of CK2 against endoplasmic reticulum stress in pancreatic β cells.Diabetology international · 2025Article
- Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket.iScience · 2024Article
- Is It Still Possible to Think about HSP70 as a Therapeutic Target in Onco-Hematological Diseases?Biomolecules · 2023Review
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target.Oncogene · 2022Review
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- Hybrid Drugs-A Strategy for Overcoming Anticancer Drug Resistance?Molecules (Basel, Switzerland) · 2021Review
- Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.International journal of molecular sciences · 2021Review
- Mechanistic Basis for In Vivo Therapeutic Efficacy of CK2 Inhibitor CX-4945 in Acute Myeloid Leukemia.Cancers · 2021Article
- Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945.Cells · 2021Article
- Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas.Cancer science · 2021Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Transcriptional Regulation of PIK3CD and PIKFYVE in T-Cell Acute Lymphoblastic Leukemia by IKAROS and Protein Kinase CK2.International journal of molecular sciences · 2021Article
- Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.Oncogenesis · 2020Article
- Article
- Influence of Casein kinase II inhibitor CX-4945 on BCL6-mediated apoptotic signaling in B-ALL in vitro and in vivo.BMC cancer · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutively active casein kinase 2 (CK2) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL). CK2 phosphorylates PTEN (phosphatase and tensin homolog) tumor suppressor, resulting in PTEN stabilization and functional inactivation. Downregulation of PTEN activity has an impact on PI3K/Akt/mTOR signaling, which is of fundamental importance for T-ALL cell survival. These observations lend compelling weight to the application of CK2 inhibitors in the therapy of T-ALL. Here, we have analyzed the therapeutic potential of CX-4945-a novel, highly specific, orally available, ATP-competitive inhibitor of CK2α. We show that CX-4945 treatment induced apoptosis in T-ALL cell lines and patient T lymphoblasts. CX-4945 downregulated PI3K/Akt/mTOR signaling in leukemic cells. Notably, CX-4945 affected the unfolded protein response (UPR), as demonstrated by a significant decrease in the levels of the main UPR regulator GRP78/BIP, and led to apoptosis via upregulation of the ER stress/UPR cell death mediators IRE1α and CHOP. In vivo administration of CX-4945 to a subcutaneous xenotransplant model of human T-ALL significantly delayed tumor growth. Our findings indicate that modulation of the ER stress/UPR signaling through CK2 inhibition could be exploited for inducing apoptosis in T-ALL cells and that CX-4945 may be an efficient treatment for those T-ALLs displaying upregulation of CK2α/PI3K/Akt/mTOR signaling.
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.