Sphingolipid metabolism determines the therapeutic efficacy of nanoliposomal ceramide in acute myeloid leukemia

Author:

Barth Brian M.123ORCID,Wang Weiyuan1,Toran Paul T.1,Fox Todd E.45,Annageldiyev Charyguly23,Ondrasik Regina M.23,Keasey Nicole R.23,Brown Timothy J.236ORCID,Devine Viola G.23,Sullivan Emily C.1,Cote Andrea L.1,Papakotsi Vasiliki1,Tan Su-Fern2378,Shanmugavelandy Sriram S.4,Deering Tye G.5,Needle David B.1ORCID,Stern Stephan T.9,Zhu Junjia10,Liao Jason10,Viny Aaron D.11ORCID,Feith David J.2378,Levine Ross L.11,Wang Hong-Gang3412ORCID,Loughran Thomas P.2378,Sharma Arati234,Kester Mark345813,Claxton David F.23ORCID

Affiliation:

1. Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH;

2. Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA;

3. Penn State Hershey Cancer Institute, Hershey, PA;

4. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA;

5. Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA;

6. Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX;

7. Division of Hematology and Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA;

8. University of Virginia Cancer Center, Charlottesville, VA;

9. Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., National Cancer Institute–Frederick National Laboratory for Cancer Research, Frederick, MD;

10. Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA;

11. Human Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;

12. Pediatric Molecular Oncology Program, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA; and

13. nanoSTAR Institute, University of Virginia, Charlottesville, VA

Abstract

Key Points Distinct sphingolipid metabolism of AML with MDS-related changes defines unique sensitivity to nanoliposomal C6-ceramide. Vinblastine alters sphingolipid metabolism to enhance the sensitivity of AML to nanoliposomal C6-ceramide.

Publisher

American Society of Hematology

Subject

Hematology

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