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

Blood Adv. 2019 Sep 10;3(17):2598-2603. doi: 10.1182/bloodadvances.2018021295.

Brian M Barth^{1

2

3}, Weiyuan Wang¹, Paul T Toran¹, Todd E Fox^{4

5}, Charyguly Annageldiyev^{2

3}, Regina M Ondrasik^{2

3}, Nicole R Keasey^{2

3}, Timothy J Brown^{2

3

6}, Viola G Devine^{2

3}, Emily C Sullivan¹, Andrea L Cote¹, Vasiliki Papakotsi¹, Su-Fern Tan^{2

3

7

8}, Sriram S Shanmugavelandy⁴, Tye G Deering⁵, David B Needle¹, Stephan T Stern⁹, Junjia Zhu¹⁰, Jason Liao¹⁰, Aaron D Viny¹¹, David J Feith^{2

3

7

8}, Ross L Levine¹¹, Hong-Gang Wang^{3

4

12}, Thomas P Loughran Jr^{2

3

7

8}, Arati Sharma^{2

3

4}, Mark Kester^{3

4

5

8

13}, David F Claxton^{2

3}

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

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.