ArticleLeukemia2016
The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 101 citations in OpenAlex.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Targeting CDK11 in Rhabdoid Tumor of the Kidney.Cancers · 2026Article
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1.Cancer cell international · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Isoginkgetin Induces Caspase Cascade Activation and Cell Apoptosis via JNK Signaling in Oral Cancer.Journal of Cancer · 2025Article
- Assessment of SF3B1 Expression as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Stage III Triple-Negative Breast Cancer.Reports of biochemistry & molecular biology · 2025Article
- Tipping the balance of cell death: alternative splicing as a source of MCL-1S in cancer.Cell death & disease · 2024Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- Synthesis and antiproliferative activity of a tetrahydrofuran analog of FR901464.Bioorganic & medicinal chemistry letters · 2024Article
- Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.International journal of biological sciences · 2024Article
- Article
- PHF5A as a new OncoTarget and therapeutic prospects.Heliyon · 2023Review
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- Review
- Targeted splicing therapy: new strategies for colorectal cancer.Frontiers in oncology · 2023Review
- Research progress and therapeutic prospect of PHF5A acting as a new target for malignant tumors.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Myelodysplastic syndromes.Nature reviews. Disease primers · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
The pro-survival Bcl-2 family member Mcl-1 is expressed in chronic lymphocytic leukaemia (CLL), with high expression correlated with progressive disease. The spliceosome inhibitor spliceostatin A (SSA) is known to regulate Mcl-1 and so here we assessed the ability of SSA to elicit apoptosis in CLL. SSA induced apoptosis of CLL cells at low nanomolar concentrations in a dose- and time-dependent manner, but independently of SF3B1 mutational status, IGHV status and CD38 or ZAP70 expression. However, normal B and T cells were less sensitive than CLL cells (P=0.006 and P<0.001, respectively). SSA altered the splicing of anti-apoptotic MCL-1(L) to MCL-1(s) in CLL cells coincident with induction of apoptosis. Overexpression studies in Ramos cells suggested that Mcl-1 was important for SSA-induced killing since its expression inversely correlated with apoptosis (P=0.001). IL4 and CD40L, present in patient lymph nodes, are known to protect tumour cells from apoptosis and significantly inhibited SSA, ABT-263 and ABT-199 induced killing following administration to CLL cells (P=0.008). However, by combining SSA with the Bcl-2/Bcl-x(L) antagonists ABT-263 or ABT-199, we were able to overcome this pro-survival effect. We conclude that SSA combined with Bcl-2/Bcl-x(L) antagonists may have therapeutic utility for 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.