EJHaem · 2025
Adipocytes Impair Mitoxantrone Cytotoxicity Against Acute Lymphoblastic Leukemia.
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Cohen Michael, Orgel Etan, Nevarez-Mejia Jessica, Chen Ting, Neely Michael, Louie Stan, Mittelman Steven D
Аннотация
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.
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.