Abstract
Abstract Acute myeloid leukemia (AML) is a disease characterized by uncontrolled proliferation of immature myeloid cells in the blood and bone marrow. Patient 5-year survival rate is only 26%, and there have been no significant treatment advances for decades. Therefore, there is an urgent need to identify novel therapeutic targets. We have previously shown that acid ceramidase (AC) is upregulated in AML and high AC activity correlates with poor patient survival. We continue to validate AC as a potential therapeutic target in AML through inhibitor screening and characterization. We utilize viability assays, enzyme activity assays, Western blotting, qPCR, lipidomics, and flow cytometry to examine the effects of inhibitors on AML cell lines, patient samples, and normal controls. We have found that a newly developed selective AC inhibitor, SACLAC, significantly reduces viability of AML cells with an EC50 of approximately 3 μM, with limited effect on normal cells at an EC50 of approximately 13 μM. Treatment of AML cell lines with SACLAC effectively blocks AC activity, induces a drastic decrease of sphingosine 1-phosphate, and a 2.5-fold increase in total ceramide levels. Ongoing studies continue to explore the mechanistic basis for the loss of viability. These data support the investigation of AC as a therapeutic target in AML and define SACLAC as a potent and selective inhibitor that presents promise for preclinical studies and future clinical development. Citation Format: Jennifer M. Pearson, Su-Fern Tan, Arati Sharma, Todd E. Fox, Jose Luis Abad, Gemma Fabrias, David F. Claxton, David J. Feith, Mark Kester, Thomas P. Loughran, Jr.. Acid ceramidase inhibition: A targeted therapy for acute myeloid leukemia [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 48.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
