Biological Findings and Clinical Outcomes in Patients Treated With R-CHOP Plus High-Dose Methotrexate as First-Line Therapy in Large B-Cell Lymphoma With Testis Involvement.

Primary testicular lymphoma (PTL) is a rare occurrence of diffuse large B-cell lymphoma (DLBCL) that accounts for 1%-2% of all cases. Nodal DLBCL with testis involvement (DLBCL-T) and PTL are associated with poor prognosis, with high incidence of central nervous system relapse. Fifteen patients (median age 60 years) with PTL (n = 5) or DLBCL-T (n = 10) received high-dose methotrexate + R-CHOP. Overall, complete response (CR) rate was 73% and overall response rate 86%. With a 3.9-year median follow-up, 100% of patients with PTL had CR and none relapsed. On the contrary, 55% of DLBCL-T patients achieved CR among which only one was still in remission at the end of follow-up. Molecular parallels between PTL and Primary CNS Lymphoma (PCNSL) suggest shared origins, urging further research for tailored treatments and enhanced understanding of these lymphomas' biology.

Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein.

Artemisinin is an anti-malarial drug that has shown anticancer properties. Recently, ferroptosis was reported to be induced by dihydroartemisinin (DHA) and linked to iron increase. In the current study, we determined the effect of DHA in leukemic cell lines on ferroptosis induction and iron metabolism and the cytoprotective effect triggered in leukemic cells. We found that treatment of DHA induces early ferroptosis by promoting ferritinophagy and subsequent iron increase. Furthermore, our study demonstrated that DHA activated zinc metabolism signaling, especially the upregulation of metallothionein (MT). Supportingly, we showed that inhibition MT2A and MT1M isoforms enhanced DHA-induced ferroptosis. Finally, we demonstrated that DHA-induced ferroptosis alters glutathione pool, which is highly dependent on MTs-driven antioxidant response. Taken together, our study indicated that DHA activates ferritinophagy and subsequent ferroptosis in AML and that MTs are involved in glutathione regenerating and antioxidant response.