ArticleCancer cell2014
Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4.
Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Bortezomib-based chemotherapy in Chinese pediatric patients with relapsed/refractory acute lymphoblastic leukemia: A single-center retrospective study.Pediatric investigation · 2026Article
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia.Scientific reports · 2025Article
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Bortezomib Is Effective in the Treatment of T Lymphoblastic Leukaemia by Inducing DNA Damage, WEE1 Downregulation, and Mitotic Catastrophe.International journal of molecular sciences · 2023Article
- Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia.Nature communications · 2023Article
- Functional, structural, and molecular characterizations of the leukemogenic driver MEF2D-HNRNPUL1 fusion.Blood · 2022Article
- Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia.Cell death discovery · 2022Article
- A T-cell independent universal cellular therapy strategy through antigen depletion.Theranostics · 2022Article
- Deubiquitinating enzyme inhibitor alleviates cyclin A1-mediated proteasome inhibitor tolerance in mixed-lineage leukemia.Cancer science · 2021Article
- Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL-AF4 fusion protein.Scientific reports · 2021Article
- EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex.Scientific reports · 2021Article
- The Role of Proteasome Inhibitors in Treating Acute Lymphoblastic Leukaemia.Frontiers in oncology · 2021Review
- MLL-Rearranged Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2020Review
- Exosomes mediate intercellular transfer of non-autonomous tolerance to proteasome inhibitors in mixed-lineage leukemia.Cancer science · 2020Article
- Article
- (Immuno)proteasomes as therapeutic target in acute leukemia.Cancer metastasis reviews · 2017Review
- Article
- The full transforming capacity of MLL-Af4 is interlinked with lymphoid lineage commitment.Blood · 2017Article
- The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma.Cell reports · 2017Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Chromosomal translocations disrupting MLL generate MLL-fusion proteins that induce aggressive leukemias. Unexpectedly, MLL-fusion proteins are rarely observed at high levels, suggesting excessive MLL-fusions may be incompatible with a malignant phenotype. Here, we used clinical proteasome inhibitors, bortezomib and carfilzomib, to reduce the turnover of endogenous MLL-fusions and discovered that accumulated MLL-fusions induce latent, context-dependent tumor suppression programs. Specifically, in MLL pro-B lymphoid, but not myeloid, leukemias, proteasome inhibition triggers apoptosis and cell cycle arrest involving activation cleavage of BID by caspase-8 and upregulation of p27, respectively. Furthermore, proteasome inhibition conferred preliminary benefit to patients with MLL-AF4 leukemia. Hence, feasible strategies to treat cancer-type and oncogene-specific cancers can be improvised through harnessing inherent tumor suppression properties of individual oncogenic fusions.
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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.