Ironomycin induces Mantle Cell Lymphoma cell death by targeting iron metabolism adicction

Mantle Cell lymphoma (MCL) remains an aggressive and incurable cancer with existing therapies, presenting a significant unmet clinical need. We evaluated the therapeutic interest of targeting iron homeostasis with Ironomycin alone and combined with ibrutinib, a BTK inhibitor accepted for the treatment of MCL patients. Patients commonly develop resistance to ibrutinib treatment. We found that ironomycin synergizes with ibrutinib to kill MCL cells even in ibrutinib-resistant cell lines. Three MCL cell lines (JEKO1, JVM2 and MAVER1) were treated with ironomycin and the BTK inhibitor ibrutinib alone or combined for 48 hours. RNA-seq analysis of the cells was performed at the end of the treatments.