ArticleOncogene2016
Elimination of chronic lymphocytic leukemia cells in stromal microenvironment by targeting CPT with an antiangina drug perhexiline.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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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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.
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Who cites it
61 citing papers in PubMed, 83 citations in OpenAlex.
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- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Darunavir analog precursors target mitochondrial metabolism in multiple myeloma and CLL.Cancer cell international · 2025Article
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- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Carnitine Shuttle and Ferroptosis in Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
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- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
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- Dysfunction of the carnitine cycle in tumor progression.Heliyon · 2024Review
- Strategic disruption of cancer's powerhouse: precise nanomedicine targeting of mitochondrial metabolism.Journal of nanobiotechnology · 2024Review
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- ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia.Leukemia · 2024Article
- Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1-mediated lipid metabolism.Clinical and translational medicine · 2024Article
- The Physiological and Pathological Role of Acyl-CoA Oxidation.International journal of molecular sciences · 2023Review
- Breast cancers as ecosystems: a metabolic perspective.Cellular and molecular life sciences : CMLS · 2023Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries and is currently incurable due, in part, to difficulty in eliminating the leukemia cells protected by stromal microenvironment. Based on previous observations that CLL cells exhibit mitochondrial dysfunction and altered lipid metabolism and that carnitine palmitoyltransferases (CPT) have a major role in transporting fatty acid into mitochondria to support cancer cell metabolism, we tested several clinically relevant inhibitors of lipid metabolism for their ability to eliminate primary CLL cells. We discovered that perhexiline, an antiangina agent that inhibits CPT, was highly effective in killing CLL cells in stromal microenvironment at clinically achievable concentrations. These effective concentrations caused low toxicity to normal lymphocytes and normal stromal cells. Mechanistic study revealed that CLL cells expressed high levels of CPT1 and CPT2. Suppression of fatty acid transport into mitochondria by inhibiting CPT using perhexiline resulted in a depletion of cardiolipin, a key component of mitochondrial membranes, and compromised mitochondrial integrity, leading to rapid depolarization and massive CLL cell death. The therapeutic activity of perhexiline was further demonstrated in vivo using a CLL transgenic mouse model. Perhexiline significantly prolonged the overall animal survival by only four drug injections. Our study suggests that targeting CPT using an antiangina drug is able to effectively eliminate leukemia cells in vivo, and is a novel therapeutic strategy for potential clinical treatment 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.