Although it remains unknown if long-term exposure of MCL cells to ibrutinib induces/selects MCL-1-overexpressing clones and leads to resistant disease, our data raise the possibility that BMI-1 inhibition not only targets tumor-initiating MCL cells but also counteracts proliferation of MCL-1-expressing ibrutinib-resistant clones. The gene discussed is BMI1; the disease is mantle cell lymphoma.