Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia via a cytotoxic integrated stress response

Abstract excerpt

Resistance to combination regimens containing the BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) is a growing clinical challenge for this extensively utilized agent. We previously established the anti-leukemic properties of ceramide, a tumor-suppressive sphingolipid, in AML and demonstrated that upregulated expression of acid ceramidase (AC), a ceramide-neutralizing enzyme, supported leukemic survival...

Topics

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• Acute Myeloid Leukemia Research
• Antineoplastic Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Drug Resistance, Neoplasm
• Histone Deacetylase Inhibitors Research
• Leukemia, Myeloid, Acute
• Protein Degradation and Inhibitors
• Sphingolipid Metabolism and Signaling

Identifiers and source

Literature Corpus work

7e431f56-276d-5638-9c85-64d8d1ca9913

DOI

10.1101/2025.06.06.657881