Co-altered genes and potential therapeutic approaches in NUP98-rearranged hematologic malignancies. (A) NUP98 fusion confers self-renewal and loss of differentiation. (B) Co-occurring alterations, including FLT3-ITD mutation, RAS mutation, and/or WT1 mutation may lead to a proliferative advantage and to hematologic malignancy. (C) Potential strategies for therapeutic targeting of hematologic malignancies with NUP98 gene fusions.