ArticleNature communications2021
Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
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- Navigating primary and secondary immunodeficiency intersections: how to find IEI hidden within SID.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Review
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- Bridging cancer therapies: the role of magnetic nanoparticles in combination cancer therapy.Discover nano · 2026Review
- Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia.Science signaling · 2026Article
- Raddeanoside R7 inhibits proliferation and migration of ovarian cancer cells through P13K-AKT signaling.Journal of ovarian research · 2026Article
- Inhibiting sirtuin-dependent DNA repair and oxidative stress responses impairs DIPG cell survival.Research square · 2025Article
- Exome sequencing reveals new insights into the germline landscape of inflammatory breast cancer among Tunisian patients.Journal of translational medicine · 2025Article
- Common origins of autoimmune diseases and lymphoid malignancies.Trends in immunology · 2025Review
- Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Regulatory mimicry of cyclin-dependent kinases by a conserved herpesvirus protein kinase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
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- LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models.Pharmaceutics · 2025Article
- Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy.Current medicinal chemistry · 2025Review
- Genomic discovery of EF-24 targets unveils antitumorigenic mechanisms in leukemia cells.PloS one · 2025Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
Current therapeutic approaches for chronic lymphocytic leukemia (CLL) focus on the suppression of oncogenic kinase signaling. Here, we test the hypothesis that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT (PI3K/AKT)-signaling pathway may be leveraged to trigger CLL cell death. Though counterintuitive, our data show that genetic hyperactivation of PI3K/AKT-signaling or blocking the activity of the inhibitory phosphatase SH2-containing-inositol-5'-phosphatase-1 (SHIP1) induces acute cell death in CLL cells. Our mechanistic studies reveal that increased AKT activity upon inhibition of SHIP1 leads to increased mitochondrial respiration and causes excessive accumulation of reactive oxygen species (ROS), resulting in cell death in CLL with immunogenic features. Our results demonstrate that CLL cells critically depend on mechanisms to fine-tune PI3K/AKT activity, allowing sustained proliferation and survival but avoid ROS-induced cell death and suggest transient SHIP1-inhibition as an unexpectedly promising concept for CLL therapy.
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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.