Adipocytes Impair Mitoxantrone Cytotoxicity Against Acute Lymphoblastic Leukemia

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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.

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