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Original Articles

Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

Jessica L. SeaDivision of Pediatric Endocrinology, UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA;

http://orcid.org/0000-0002-3812-9032 View further author information

Etan OrgelDivision of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, Los Angeles, CA, USA; ;Department of Pediatrics, University of Southern California, Los Angeles, CA, USA; View further author information

Ting ChenDivision of Pediatric Endocrinology, UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; View further author information

Rebecca L. PaszkiewiczDivision of Pediatric Endocrinology, UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; View further author information

Abigail S. KrallDepartment of Biological Chemistry and the Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA; View further author information

Matthew J. OberleyDepartment of Pediatrics, University of Southern California, Los Angeles, CA, USA; ;Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Keck School of Medicine, Los Angeles, CA, USA; View further author information

Linsey StilesDivision of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USAView further author information

Steven D. MittelmanDivision of Pediatric Endocrinology, UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Correspondence[email protected]

http://orcid.org/0000-0003-2867-1298 View further author information

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Abstract

Asparaginase (ASNase) is an integral part of pediatric induction chemotherapy that has also been shown to improve adult survival rates; however, pegylated (PEG)-ASNase induces severe hepatotoxicity in this population. Recent case reports describe the incorporation of levocarnitine (LC) supplementation into PEG-ASNase-containing induction regimens to prevent or treat hepatotoxicity. Because LC facilitates the metabolism of free fatty acids (FFA), a primary fuel source for ALL cells, LC could potentially interfere with ALL chemotherapy efficacy. To test this, we employed in vitro and in vivo models of ALL. We show in vitro that LC supplementation does not impact cytotoxicity from vincristine, daunorubicin, dexamethasone, or ASNase on human ALL cells nor lead to an increase in ALL cell metabolic rate. In vivo, we demonstrate LC does not impair PEG-ASNase monotherapy in mice with syngeneic ALL. Together, our findings show that LC supplementation is a safe strategy to prevent/reverse ASNase-induced toxicities in preclinical models.

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Acknowledgements

We thank the UCLA Mitochondrial and Metabolism Core, and the UCLA Flow Cytometry Core.

Disclosure statement

The authors have no conflicts of interest to report.

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Funding

The corresponding author is funded by an R01 from the National Institutes of Health National Cancer Institute (NIH/NCI) [Award number R01 CA201444-04].

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Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

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Levocarnitine does not impair chemotherapy cytotoxicity against acute lymphoblastic leukemia

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