Primary mediastinal large B cell lymphoma (PMBCL) is an aggressive large B cell lymphoma originating in the mediastinum, that mainly expresses B cell surface molecules, such as CD19, CD20, CD22, andCD79a. Clinically, they are characterized by rapidly increasing anterior mediastinal masses, which can cause compression of the surrounding tissues. The diagnosis of PMBCL mainly depends on the pathological features, imaging examination and clinical features. Currently, the most commonly used therapeutic regimens are R-CHOP and R-EPOCH. Radiotherapy is beneficial in some patients, but it can also lead to long-term toxicity. The research and development of novel therapies are ongoing, and some studies have achieved encouraging results, including those conducted on chimeric antigen receptor-modified T (CAR-T) cell therapy and anti-PD-1 drugs. However, randomized controlled trials with larger sample sizes are still needed. Positron emission tomography-computed tomography (PET-CT) is mainly used to assess the curative effect after treatment and to guide the subsequent treatment strategy.

Background Doxorubicin (DOX) is widely used in lymphoma, myeloma, breast cancer, and other malignant tumors, and it significantly improves the prognosis of these patients. However, its side effects, especially cardiotoxicity, must be taken seriously. Studies have shown that liposome doxorubicin (L-DOX), compared with DOX, has increased anti-tumor activity and decreased cardiac toxicity. Our aim is to investigate the mechanism of myocardial injury in mice caused by these two drugs, to identify potential mitigation strategies. Methods In this study, mice or HL-1 cells were treated with DOX or L-DOX, and the cardiac morphology, hemodynamic effect, laboratory examination, and expression of ferritinophagy-related proteins were compared with the control group. Results DOX significantly induced myocardial cell death, while L-DOX had little effect on myocardial injury. Additionally, DOX significantly increased the level of autophagy and ferroptosis in cardiac myocytes. Further analysis revealed that NCOA4-mediated ferritinophagy played a key role in the mechanism of doxorubicin-induced cardiotoxicity (DIC). Importantly, the addition of ferrostatin-1 (a ferroptosis inhibitor) was able to rescue DIC. In contrast, L-DOX reduced the damage to cardiac myocytes by reducing ferritinophagy. Conclusion We have found that a significant relationship between the mechanism of DIC and NCOA4-mediated ferritinophagy. L-DOX has been shown to reduce the damage to myocardial cells by reducing NCOA4-mediated ferritinophagy. Thus, NCOA4 has the potential to be a drug target for the cardiac protection of DIC. However, further research is need to investigate the specific role of NCOA4 in the pathogenesis of DIC.