ArticleBlood2014
BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia.Leukemia · 2026Review
- The miRNA Landscape of Leukemia - Cellular Actions to Therapy through Molecular Mechanisms.Cell biochemistry and biophysics · 2025Review
- CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells.Cell death discovery · 2025Article
- BCR::ABL1 Proteolysis-targeting chimeras (PROTACs): The new frontier in the treatment of PhLeukemia · 2024Review
- The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.Blood · 2024Article
- Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.Cancer research · 2023Article
- Cyclin-dependent kinase inhibitors in malignant hematopoiesis.Frontiers in oncology · 2022Review
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- Review
- Declaration of Bcr-Abl1 independence.Leukemia · 2020Review
- Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy.Cells · 2019Review
- Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib.Blood advances · 2019Article
- Inhibition of interleukin-1 receptor-associated kinase-1 is a therapeutic strategy for acute myeloid leukemia subtypes.Leukemia · 2018Article
- The prognostic potential of coilin in association with p27 expression in pediatric acute lymphoblastic leukemia for disease relapse.Cancer cell international · 2018Article
- p27 in FLT3-driven acute myeloid leukemia: many roads lead to ruin.Haematologica · 2017Article
- CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27Haematologica · 2017Article
- Identification of Interleukin-1 by Functional Screening as a Key Mediator of Cellular Expansion and Disease Progression in Acute Myeloid Leukemia.Cell reports · 2017Article
- Mechanisms of p53 Functional De-Regulation: Role of the IκB-α/p53 Complex.International journal of molecular sciences · 2016Review
- The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase.BMC cancer · 2016Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Recent studies have revealed that p27, a nuclear cyclin-dependent kinase (Cdk) inhibitor and tumor suppressor, can acquire oncogenic activities upon mislocalization to the cytoplasm. To understand how these antagonistic activities influence oncogenesis, we dissected the nuclear and cytoplasmic functions of p27 in chronic myeloid leukemia (CML), a well-characterized malignancy caused by the BCR-ABL1 tyrosine kinase. p27 is predominantly cytoplasmic in CML and nuclear in normal cells. BCR-ABL1 regulates nuclear and cytoplasmic p27 abundance by kinase-dependent and -independent mechanisms, respectively. p27 knockdown in CML cell lines with predominantly cytoplasmic p27 induces apoptosis, consistent with a leukemogenic role of cytoplasmic p27. Accordingly, a p27 mutant (p27(CK-)) devoid of Cdk inhibitory nuclear functions enhances leukemogenesis in a murine CML model compared with complete absence of p27. In contrast, p27 mutations that enhance its stability (p27(T187A)) or nuclear retention (p27(S10A)) attenuate leukemogenesis over wild-type p27, validating the tumor-suppressor function of nuclear p27 in CML. We conclude that BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. These findings suggest that cytoplasmic mislocalization of p27 despite BCR-ABL1 inhibition by tyrosine kinase inhibitors may contribute to drug resistance, and effective therapeutic strategies to stabilize nuclear p27 must also prevent cytoplasmic mislocalization.
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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.