ArticleOncotarget2016
Acid ceramidase is upregulated in AML and represents a novel therapeutic target.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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The trial behind it
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Who cites it
66 citing papers in PubMed, 93 citations in OpenAlex.
- ZMAT3 alleviates cell death in Fanconi anemia via adaptation of sphingolipid metabolism.Science advances · 2026Article
- Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia.Blood neoplasia · 2026Article
- The small GTPase ARF6 regulates sphingolipid homeostasis and supports proliferation in acute myeloid leukemia.Haematologica · 2026Article
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Plasma lipid levels predict chemotherapy response and survival in acute myeloid leukemia.Blood · 2025Article
- Metabolic Signature ofJournal of personalized medicine · 2025Review
- Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed/refractory multiple myeloma.Haematologica · 2025Article
- Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment.HemaSphere · 2025Review
- Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review.Cancers · 2025Review
- Phosphatidic acid phosphatase LPIN1 in phospholipid metabolism and stemness in hematopoiesis and AML.HemaSphere · 2025Article
- Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers.International journal of molecular sciences · 2025Article
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Combating Acute Myeloid Leukemia via Sphingosine Kinase 1 Inhibitor-Nanomedicine Combination Therapy with Cytarabine or Venetoclax.Pharmaceutics · 2024Article
- The Role of Ceramide and Sphingolipid Metabolism in Cancer Therapeutics.Journal of oncology research and therapy · 2024Article
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Acid ceramidase expression reduces IFNγ secretion by mouse CD4Frontiers in immunology · 2024Article
- Acid ceramidase regulates innate immune memory.Cell reports · 2023Article
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 11 institutions in 3 countries.
Funding
Abstract
There is an urgent unmet need for new therapeutics in acute myeloid leukemia (AML) as standard therapy has not changed in the past three decades and outcome remains poor for most patients. Sphingolipid dysregulation through decreased ceramide levels and elevated sphingosine 1-phosphate (S1P) promotes cancer cell growth and survival. Acid ceramidase (AC) catalyzes ceramide breakdown to sphingosine, the precursor for S1P. We report for the first time that AC is required for AML blast survival. Transcriptome analysis and enzymatic assay show that primary AML cells have high levels of AC expression and activity. Treatment of patient samples and cell lines with AC inhibitor LCL204 reduced viability and induced apoptosis. AC overexpression increased the expression of anti-apoptotic Mcl-1, significantly increased S1P and decreased ceramide. Conversely, LCL204 induced ceramide accumulation and decreased Mcl-1 through post-translational mechanisms. LCL204 treatment significantly increased overall survival of C57BL/6 mice engrafted with leukemic C1498 cells and significantly decreased leukemic burden in NSG mice engrafted with primary human AML cells. Collectively, these studies demonstrate that AC plays a critical role in AML survival through regulation of both sphingolipid levels and Mcl-1. We propose that AC warrants further exploration as a novel therapeutic target in AML.
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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.