Absence of tumor suppressors FoxO3a and PTEN in the nucleus could be an explanation for ibrutinib resistance in 2p+ CLL patients who overexpress XPO1 and why selinexor and next-generation XPO1 inhibitors seem to be efficient in preclinical CLL and MCL models where it reduces NFκB binding to DNA (92, 130–132). This evidence concerns the gene FOXO3 and B-cell chronic lymphocytic leukemia.