ArticleThe Journal of clinical investigation2015
Inhibition of IRAK1/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- An integrative machine learning and structure-driven drug repositioning strategy for human IRAK4-targeted cancer therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- The Direction of Modern Therapies in Waldenström Macroglobulinaemia.Journal of cellular and molecular medicine · 2025Review
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Review
- Emerging trends in IRAK-4 kinase research.Molecular biology reports · 2023Review
- Review
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- miRNAs in Lymphocytic Leukaemias-The miRror of Drug Resistance.International journal of molecular sciences · 2022Review
- Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors.Nature communications · 2022Article
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- E3 ubiquitin ligases in the acute leukemic signaling pathways.Frontiers in physiology · 2022Review
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- IRAK1-regulated IFN-γ signaling induces MDSC to facilitate immune evasion in FGFR1-driven hematological malignancies.Molecular cancer · 2021Article
- Inhibition of IRAK1/4 enhances the antitumor effect of lenvatinib in anaplastic thyroid cancer cells.Cancer science · 2021Article
- Article
- DNA methylation-mediated silencing of microRNA-204 enhances T cell acute lymphoblastic leukemia by up-regulating MMP-2 and MMP-9 via NF-κB.Journal of cellular and molecular medicine · 2021Article
- IRAK inhibitor can improve insulin sensitivity in insulin-resistant mice fed with a high-fat diet.Asian biomedicine : research, reviews and news · 2020Article
- CSF-1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Signaling via the MyD88/IRAK pathway in T cells is indispensable for cell survival; however, it is not known whether this pathway functions in the progression of T acute lymphoblastic leukemia (T-ALL). Here, we determined that compared with thymic and peripheral T cells, T-ALL cells from patients have elevated levels of IRAK1 and IRAK4 mRNA as well as increased total and phosphorylated protein. Targeted inhibition of IRAK1 and IRAK4, either with shRNA or with a pharmacological IRAK1/4 inhibitor, dramatically impeded proliferation of T-ALL cells isolated from patients and T-ALL cells in a murine leukemia model; however, IRAK1/4 inhibition had little effect on cell death. We screened several hundred FDA-approved compounds and identified a set of drugs that had enhanced cytotoxic activity when combined with IRAK inhibition. Administration of an IRAK1/4 inhibitor or IRAK knockdown in combination with either ABT-737 or vincristine markedly reduced leukemia burden in mice and prolonged survival. IRAK1/4 signaling activated the E3 ubiquitin ligase TRAF6, increasing K63-linked ubiquitination and enhancing stability of the antiapoptotic protein MCL1; therefore, IRAK inhibition reduced MCL1 stability and sensitized T-ALL to combination therapy. These studies demonstrate that IRAK1/4 signaling promotes T-ALL progression through stabilization of MCL1 and suggest that impeding this pathway has potential as a therapeutic strategy to enhance chemotherapeutic efficacy.
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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.