Figure 3.

Therapeutic options to target oncogenic condensates in AML. (A) Leukemic cells harboring pathological condensates can be targeted by drugs targeting condensate protein/RNA components or their posttranscriptional/ translational modifications. Drug partitioning into condensates can induce the restoration of physiological condensates, alter condensate function or dissolve pathological condensates, and ultimately lead to terminal differentiation. (B) The histone deacetylase EP300 localizes to nuclear condensates and treatment with the EP300 inhibitor A-485 leads to dissolution of condensates into more numerous and smaller structures. As EP300 interacts with NUP98-fusion proteins that form pathological condensates, A-485 treatment might affect the formation of NUP98-fusion condensates with potential implications in therapy development. (C) Inhibition of Menin leads to loss of the Menin-MLL1 interaction, which is required for transcriptional activity of target HOX genes in many AML subtypes. (D) In PML::RARA-driven APL, de-neddylation of the RARA moiety by MLN4924 leads to the release of the fusion protein from chromatin and restoration of PML bodies. Induction of proteasomal degradation of PML::RARA by ATRA/ATO causes restoration of physiological PML bodies. AML = acute myeloid leukemia; ATO = arsenic trioxide; ATRA = all-trans retinoic acid; PML = promyelocytic leukemia protein.