ArticleLeukemia2017
Casein kinase 2 controls the survival of normal thymic and leukemic γδ T cells via promotion of AKT signaling.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications.Discover oncology · 2025Review
- Characterization ofInternational journal of molecular sciences · 2025Article
- Akt isoforms in the immune system.Frontiers in immunology · 2022Review
- The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma.Cancers · 2021Review
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- The role of the oncogenic Rab35 in cancer invasion, metastasis, and immune evasion, especially in leukemia.Small GTPases · 2020Review
- Article
- γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer.Nature reviews. Cancer · 2019Review
- MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1.Science immunology · 2018Article
- Therapeutic targeting of CK2 in acute and chronic leukemias.Leukemia · 2018Review
- Multifaceted CK2 in malignant and healthy T cells.Oncotarget · 2017Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein kinase 2 (CK2) is a serine/threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage. γδ thymocytes display higher (and T-cell receptor inducible) CK2 activity than their αβ counterparts, and are strikingly sensitive to death upon CK2 inhibition. Mechanistically, we show that CK2 regulates the pro-survival AKT signaling pathway in γδ thymocytes and, importantly, also in γδ T-cell acute lymphoblastic leukemia (T-ALL) cells. When compared with healthy thymocytes or leukemic αβ T cells, γδ T-ALL cells show upregulated CK2 activity, potentiated by CD27 costimulation, and enhanced apoptosis upon CK2 blockade using the chemical inhibitor CX-4945. Critically, this results in inhibition of tumor growth in a xenograft model of human γδ T-ALL. These data identify CK2 as a novel survival determinant of both healthy and leukemic γδ T cells, and may thus greatly impact their therapeutic manipulation.
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Registered trials
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