Adipocytes Impair Mitoxantrone Cytotoxicity Against Acute Lymphoblastic Leukemia

  • EJHaem. 2025 Aug 30;6(5):e70140. doi: 10.1002/jha2.70140.
Michael Cohen  1 ,  Etan Orgel  2  3 ,  Jessica Nevarez-Mejia  1 ,  Ting Chen  1 ,  Michael Neely  3  4 ,  Stan Louie  5 ,  Steven D Mittelman  1
Affiliations
  • 1. Division of Pediatric Endocrinology UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine University of California Los Angeles Los Angeles California USA.
  • 2. Cancer and Blood Disease Institute Children's Hospital Los Angeles Los Angeles California USA.
  • 3. Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles California USA.
  • 4. Laboratory of Applied Pharmacokinetics and Bioinformatics The Saban Research Institute Children's Hospital Los Angeles Los Angeles California USA.
  • 5. Mann School of Pharmacy and Pharmaceutical Sciences Keck School of Medicine University of Southern California Los Angeles California USA.
PMID: 40896243 DOI: 10.1002/jha2.70140
Abstract

Introduction: Obesity contributes to poorer clinical outcomes in patients with acute lymphoblastic leukemia. We have shown that adipocytes cause anthracycline resistance by absorbing and metabolizing them into less-active alcohol metabolites.

Methods: We hypothesized that mitoxantrone, which has a similar cytotoxic mechanism to anthracyclines but is metabolized through different pathways, might overcome this adipocyte-mediated chemoresistance. We treated human BV173 acute lymphoblastic leukemia cells with daunorubicin and mitoxantrone that had been incubated with or without 3T3-L1 adipocytes.

Results: Contrary to our hypothesis, adipocytes induced similar chemoresistance to both drugs.

Conclusion: Mitoxantrone is unlikely to be an attractive alternative to overcome adipocyte-mediated anthracycline resistance in patients with obesity.

Trial registration: The authors have confirmed clinical trial registration is not needed for this submission.

Keywords
acute leukemia; chemotherapy; drug resistance; pharmacokinetics.
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