Genetic predisposition of Asparaginase-induced hypertriglyceridemia in children with acute lymphoblastic leukemia: Two case reports and review of literature

doi:10.5409/wjcp.120927

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World Journal of Clinical Pediatrics

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2219-2808

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Pediatr. Sep 9, 2026; 15(3): 120927
Published online Sep 9, 2026. doi: 10.5409/wjcp.120927

Genetic predisposition of Asparaginase-induced hypertriglyceridemia in children with acute lymphoblastic leukemia: Two case reports and review of literature

Maria Krivosheina, Victoria Bakaleiko, Yulia Toshina, George Baratashvili, Polina Sokolnikova, Olga V Kalinina, Asiiat Alieva, Yulia Dinikina, Anna A Kostareva

Maria Krivosheina, Scientific Research Laboratory of Metabolic and Metabolic Profiling of Vascular Biology, Institute of Molecular Biology and Genetics, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

Victoria Bakaleiko, Center for Atherosclerosis and Lipid Metabolism Disorders, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

Yulia Toshina, Yulia Dinikina, Department of Pediatric Oncohematology and BMT, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

George Baratashvili, Department of Gravity Surgery, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

Polina Sokolnikova, Institute of Molecular Biology and Genetics, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

Olga V Kalinina, Institute of Molecular Biology and Genetics, Department of Laboratory Medicine with Clinic, Department of Molecular Medicine and Cellular Biology, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia

Asiiat Alieva, Center for Atherosclerosis and Lipid Metabolism Disorders, Research Laboratory of Lipid Metabolism Disorders and Atherosclerosis, Institute of Metabolic Syndrome, Almazov National Medical Research Center, Saint-Petersburg 197341, Russia

Anna A Kostareva, Institute of Molecular Biology and Genetics, Department of Molecular Medicine and Cellular Biology, Institution of Medical Education, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia

Co-corresponding authors: Olga V Kalinina and Anna A Kostareva.

Author contributions: Krivosheina M analyzed and interpreted the data, drafted the initial manuscript; Bakaleiko V, Toshina Y, and Baratashvili G collected analyzed and interpreted the data; Sokolnikova P performed molecular genetic testing; Kalinina OV contributed to project administration acquisition; Kostareva AA conceptualized the study, analyzed and interpreted the data, suggested the idea for the manuscript, drafted the initial manuscript, and approved the final version for publication; Dinikina Y and Alieva A collected and processed material, drafted the text of the manuscript, edited the manuscript; Kalinina OV, Kostareva AA and Dinikina Y have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation; Kalinina OV and Kostareva AA have played important and indispensable roles in the manuscript preparation as the co-corresponding authors; and all authors contributed to manuscript editing and approved final version of the manuscript.

Supported by the Ministry of Science and Higher Education of the Russian Federation, No. 075-15-2022-301.

Informed consent statement: Informed written consent was obtained from the patients for publication of this report.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

Corresponding author: Anna A Kostareva, MD, Institute of Molecular Biology and Genetics, Department of Molecular Medicine and Cellular Biology, Institution of Medical Education, Almazov National Medical Research Centre, Akkuratova Street 2, Saint-Petersburg 197341, Russia. anna.kostareva@ki.se

Received: March 19, 2026
Revised: April 25, 2026
Accepted: May 18, 2026
Published online: September 9, 2026
Processing time: 143 Days and 3.1 Hours

Abstract

BACKGROUND

Asparaginase (ASP) is an essential antitumor agent of acute lymphoblastic leukemia (ALL) in children. Hypertriglyceridemia (HTG) represents one of several ASP-associated toxicities, alongside with hypersensitivity reactions, pancreatitis, liver dysfunction, and thrombotic events. HTG may necessitate immediate therapy modification and can lead to life-threatening complications that contraindicate further anticancer treatment. However, the clinical and genetic mechanisms underlying this condition remain poorly understood.

CASE SUMMARY

We report two rare cases of severe HTG in pediatric patients with B-ALL following treatment with pegylated ASP (PEG-ASP). To investigate the genetic basis of this susceptibility, we performed genetic testing using a targeted gene panel for hyperlipidemia and identified several potential disease-related variants associated with inherited dyslipidemia. Although the functional and causal roles of these variants require further validation, we hypothesize that they contributed substantially to the development of HTG in these patients.

CONCLUSION

Genetic factors may predispose to HTG during PEG-ASP therapy; with further evidence, genetic testing might be considered before ASP treatment

Keywords: Children; Acute leukemia; Asparaginase; Toxicity; Hypertriglyceridemia; Genetics; Clinical testing; Case report

Core Tip: Pegylated (PEG) asparaginase (ASP) is a key chemotherapy agent used in pediatric acute lymphoblastic leukemia treatment protocols. This modified form of ASP exhibits prolonged activity and reduced immunogenicity, contributing to its therapeutic efficacy and dosing convenience. However, PEG-ASP therapy can lead to various toxicities, including hypertriglyceridemia (HTG). Several genes involved in triglyceride (TG) metabolism are known to influence susceptibility to this condition, with genetic variants potentially predisposing individuals to elevated TG levels. Based on the two cases presented here, we hypothesize that genetic factors may contribute to HTG in certain pediatric patients receiving PEG-ASP therapy.