ArticleLeukemia2015
Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Second-Generation Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response: A Systematic Review and a Meta-Analysis.Computational and mathematical methods in medicine · 2021Pooled it
- A Novel CIP2A and BCL-XL Clinical Diagnostic Toolkit to Predict Disease Progression and Treatment-Free Remission in Chronic Myeloid Leukaemia.International journal of molecular sciences · 2026Article
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITDCell communication and signaling : CCS · 2024Article
- Phosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy.Journal of cancer immunology · 2024Article
- Molecular mechanism of phosphopeptide neoantigen immunogenicity.Nature communications · 2023Article
- Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.Nature communications · 2023Article
- From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.Frontiers in genetics · 2023Review
- Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia.Cancers · 2021Article
- Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.The Journal of biological chemistry · 2020Article
- Somatic variants in epigenetic modifiers can predict failure of response to imatinib but not to second-generation tyrosine kinase inhibitors.Haematologica · 2019Article
- Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia.Cancers · 2019Article
- Targeting SET to restore PP2A activity disrupts an oncogenic CIP2A-feedforward loop and impairs triple negative breast cancer progression.EBioMedicine · 2019Article
- PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells.Science translational medicine · 2018Article
- CIP2A- and SETBP1-mediated PP2A inhibition reveals AKT S473 phosphorylation to be a new biomarker in AML.Blood advances · 2018Article
- Article
- [ARTICLE WITHDRAWN] Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184.Oncology research · 2018Article
- Article
- High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia.Leukemia · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome.
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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.