ArticleBlood2012
Overexpression of TCL1 activates the endoplasmic reticulum stress response: a novel mechanism of leukemic progression in mice.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
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- Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viable mutations of mouse midnolin suppress B cell malignancies.The Journal of experimental medicine · 2024Article
- Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice.International journal of molecular sciences · 2023Article
- Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa Pathway in Mice.Journal of clinical medicine · 2023Article
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- XBP1 modulates endoplasmic reticulum and mitochondria crosstalk via regulating NLRP3 in renal ischemia/reperfusion injury.Cell death discovery · 2023Article
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- Decoding endoplasmic reticulum stress signals in cancer cells and antitumor immunity.Trends in cancer · 2022Review
- Loss of AID exacerbates the malignant progression of CLL.Leukemia · 2022Article
- Targeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemia.Medical oncology (Northwood, London, England) · 2022Article
- Review
- Integrated profiling of endoplasmic reticulum stress-related DERL3 in the prognostic and immune features of lung adenocarcinoma.Frontiers in immunology · 2022Article
- Review
- When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies.Reviews of physiology, biochemistry and pharmacology · 2021Review
- O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers.Frontiers in immunology · 2021Review
- Development of Tumor-Targeting IRE-1 Inhibitors for B-cell Cancer Therapy.Molecular cancer therapeutics · 2020Article
- MUC1 oncoprotein mitigates ER stress via CDA-mediated reprogramming of pyrimidine metabolism.Oncogene · 2020Article
- Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) represents 30% of adult leukemia. TCL1 is expressed in ~ 90% of human CLL. Transgenic expression of TCL1 in murine B cells (Eμ-TCL1) results in mouse CLL. Here we show for the first time that the previously unexplored endoplasmic reticulum (ER) stress response is aberrantly activated in Eμ-TCL1 mouse and human CLL. This includes activation of the IRE-1/XBP-1 pathway and the transcriptionally up-regulated expression of Derlin-1, Derlin-2, BiP, GRP94, and PDI. TCL1 associates with the XBP-1 transcription factor, and causes the dysregulated expression of the transcription factors, Pax5, IRF4, and Blimp-1, and of the activation-induced cytidine deaminase. In addition, TCL1-overexpressing CLL cells manufacture a distinctly different BCR, as we detected increased expression of membrane-bound IgM and altered N-linked glycosylation of Igα and Igβ, which account for the hyperactive BCR in malignant CLL. To demonstrate that the ER stress-response pathway is a novel molecular target for the treatment of CLL, we blocked the IRE-1/XBP-1 pathway using a novel inhibitor, and observed apoptosis and significantly stalled growth of CLL cells in vitro and in mice. These studies reveal an important role of TCL1 in activating the ER stress response in support for malignant progression of CLL.
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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.