Cohen Michael, Orgel Etan, Nevarez-Mejia Jessica, Chen Ting, Neely Michael, Louie Stan, Mittelman Steven D
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.
Cancer and Blood Disease Institute Children's Hospital Los Angeles Los Angeles California USA.
EJHaem. 2025 Aug 30;6(5):e70140. doi: 10.1002/jha2.70140. eCollection 2025 Oct.
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.
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.
Contrary to our hypothesis, adipocytes induced similar chemoresistance to both drugs.
Mitoxantrone is unlikely to be an attractive alternative to overcome adipocyte-mediated anthracycline resistance in patients with obesity.
The authors have confirmed clinical trial registration is not needed for this submission.
肥胖会导致急性淋巴细胞白血病患者的临床预后较差。我们已经表明，脂肪细胞通过吸收蒽环类药物并将其代谢为活性较低的醇类代谢物而导致蒽环类药物耐药。
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，但通过不同途径代谢，可能会克服这种脂肪细胞介导的化疗耐药性。我们用柔红霉素和米托蒽醌处理人BV173急性淋巴细胞白血病细胞，这些药物已与3T3-L1脂肪细胞一起或未与3T3-L1脂肪细胞一起孵育。
与我们的假设相反，脂肪细胞对两种药物均诱导出相似的化疗耐药性。
米托蒽醌不太可能成为克服肥胖患者脂肪细胞介导的蒽环类药物耐药性的有吸引力的替代药物。
作者已确认本提交内容无需临床试验注册。
