Adipocytes Impair Mitoxantrone Cytotoxicity Against Acute Lymphoblastic Leukemia

IF 1.2

EJHaem Pub Date : 2025-08-30 DOI:10.1002/jha2.70140

Michael Cohen, Etan Orgel, Jessica Nevarez-Mejia, Ting Chen, Michael Neely, Stan Louie, Steven D. Mittelman

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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.

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脂肪细胞损害米托蒽醌对急性淋巴细胞白血病的细胞毒性

肥胖导致急性淋巴细胞白血病患者临床预后较差。我们已经证明，脂肪细胞通过吸收和代谢成活性较低的酒精代谢物而引起蒽环类药物耐药性。方法我们假设米托蒽醌具有与蒽环类药物相似的细胞毒性机制，但通过不同的代谢途径，可能克服这种脂肪细胞介导的化学耐药。我们用柔红霉素和米托蒽醌治疗人BV173急性淋巴细胞白血病细胞，这些细胞与3T3-L1脂肪细胞孵育或不孵育。结果与我们的假设相反，脂肪细胞对两种药物产生了相似的化学耐药。结论米托蒽醌不太可能成为肥胖患者克服脂肪细胞介导的蒽环类药物耐药的理想选择。试验注册作者已确认该提交不需要临床试验注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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EJHaem

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