ArticleJournal of lipid research2019
Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation.
Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy.Frontiers in oncology · 2022Pooled it
- Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia.Blood neoplasia · 2026Article
- 7-Ketocholesterol Links Sterol Homeostasis to Hedgehog Signaling and Stress-Survival Responses in MSCs from Patients with Acute Myeloid Leukemia.International journal of molecular sciences · 2026Article
- Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments.Frontiers in pharmacology · 2026Review
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Integrated metabolomic and transcriptomic analysis identifies adipogenic differentiation of mesenchymal stem cells as a driver of chemoresistance in acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2025Article
- Identification of cell adhesion related signature for molecular subtyping and prognostic prediction in acute myeloid leukemia.Discover oncology · 2025Article
- Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed/refractory multiple myeloma.Haematologica · 2025Article
- Glycomics and Glycoproteomics Reveal Distinct Oligomannose Carriers Across Bladder Cancer Stages.International journal of molecular sciences · 2025Article
- P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome.International journal of molecular sciences · 2025Review
- Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment.HemaSphere · 2025Review
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Proteomics Analysis of Interactions between Drug-Resistant and Drug-Sensitive Cancer Cells: Comparative Studies of Monoculture and Coculture Cell Systems.Journal of proteome research · 2024Article
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- Potential role of autophagy induced by FLT3-ITD and acid ceramidase in acute myeloid leukemia chemo-resistance: new insights.Cell communication and signaling : CCS · 2022Review
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.International journal of molecular sciences · 2022Article
- Acid ceramidase targeting pyruvate kinase affected trypsinogen activation in acute pancreatitis.Molecular medicine (Cambridge, Mass.) · 2022Article
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- Alterations in sphingolipid composition and mitochondrial bioenergetics represent synergistic therapeutic vulnerabilities linked to multidrug resistance in leukemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. More than half of older AML patients fail to respond to cytotoxic chemotherapy, and most responders relapse with drug-resistant disease. Failure to achieve complete remission can be partly attributed to the drug resistance advantage of AML blasts that frequently express P-glycoprotein (P-gp), an ATP-binding cassette transporter. Our previous work showed that elevated acid ceramidase (AC) levels in AML contribute to blast survival. Here, we investigated P-gp expression levels in AML relative to AC. Using parental HL-60 cells and drug-resistant derivatives as our model, we found that P-gp expression and efflux activity were highly upregulated in resistant derivatives. AC overexpression in HL-60 conferred resistance to the AML chemotherapeutic drugs, cytarabine, mitoxantrone, and daunorubicin, and was linked to P-gp upregulation. Furthermore, targeting AC through pharmacologic or genetic approaches decreased P-gp levels and increased sensitivity to chemotherapeutic drugs. Mechanistically, AC overexpression increased NF-κB activation whereas NF-kB inhibitors reduced P-gp levels, indicating that the NF-kappaB pathway contributes to AC-mediated modulation of P-gp expression. Hence, our data support an important role for AC in drug resistance as well as survival and suggest that sphingolipid targeting approaches may also impact drug resistance in AML.
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Registered trials
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