ArticleBlood2012
Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Association of PTPN22 SNP1858 (rs2476601) and Gene SNP1123 (rs2488457) Polymorphism With Primary Immune Thrombocytopenia Susceptibility: A Meta-Analysis of Case-Control Studies and Trial Sequential Analysis.Frontiers in genetics · 2022Pooled it
- Exploring the mechanisms of baicalin in diabetic cardiomyopathy: Insights from network pharmacology and experimental validation.Biomedical reports · 2026Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Glycerophosphoinositol Promotes Apoptosis of Chronic Lymphocytic Leukemia Cells by Enhancing Bax Expression and Activation.Frontiers in oncology · 2022Article
- Influence ofFrontiers in immunology · 2021Review
- Constitutive activation of Lyn kinase enhances BCR responsiveness, but not the development of CLL in Eµ-TCL1 mice.Blood advances · 2020Article
- HSP90 overexpression potentiates the B-cell receptor and fibroblast growth factor receptor survival signals in chronic lymphocytic leukemia cells.Oncotarget · 2020Article
- Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies.Cancers · 2020Review
- Celebrating 20 Years of IGHV Mutation Analysis in CLL.HemaSphere · 2020Review
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation.Nature reviews. Immunology · 2019Review
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Autoimmunity checkpoints as therapeutic targets in B cell malignancies.Nature reviews. Cancer · 2018Review
- Identification of sequence variants influencing immunoglobulin levels.Nature genetics · 2017Article
- Targeted activation of the SHP-1/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells.Haematologica · 2017Article
- Genome-Wide Identification of Target Genes for the Key B Cell Transcription FactorFrontiers in immunology · 2017Article
- Tris (dibenzylideneacetone) dipalladium: a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells.Leukemia & lymphoma · 2016Article
- Article
- Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?International journal of hematologic oncology · 2016Review
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7 authors at 3 institutions in 2 countries.
Funding
Abstract
A polymorphic variant of the phosphatase PTPN22 has been associated with increased risk for multiple autoimmune diseases. The risk allele is thought to function by diminishing antigen-receptor signals responsible for negative selection of autoreactive lymphocytes. We now show that PTPN22 is markedly overexpressed in chronic lymphocytic leukemia (CLL), a common malignancy of autoreactive B lymphocytes. We also show that overexpression of PTPN22 significantly inhibits antigen-induced apoptosis of primary CLL cells by blocking B-cell receptor (BCR) signaling pathways that negatively regulate lymphocyte survival. More importantly, we show that PTPN22 positively regulates the antiapoptotic AKT kinase, which provides a powerful survival signal to antigen-stimulated CLL cells. This selective uncoupling of AKT from other downstream BCR signaling pathways is a result of inhibition of a negative regulatory circuit involving LYN, CD22, and SHIP. Finally, we show that PTPN22 can be effectively down-regulated by the PKC inhibitors ruboxistaurin and sotrastaurin, resulting in enhanced killing of CLL cells exposed to proapoptotic BCR stimuli. Collectively, these data suggest that PTPN22 overexpression represents a protective mechanism that allows autoantigen-activated CLL cells to escape from negative selection and indicate that this mechanism could be exploited for therapeutic purposes by targeting PTPN22 with PKC inhibitors.
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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.