Recent studies have suggested that several oncogenic and tumor-suppressive proteins carry out their functions in the context of specific membrane-less cellular compartments. As these compartments, generally referred to as onco-condensates, are specific to tumor cells and are tightly linked to disease development, the mechanisms of their formation and maintenance have been intensively studied. Here we review the proposed leukemogenic and tumor-suppressive activities of nuclear biomolecular condensates in acute myeloid leukemia (AML). We focus on condensates formed by oncogenic fusion proteins including nucleoporin 98 (NUP98), mixed-lineage leukemia 1 (MLL1, also known as KMT2A), mutated nucleophosmin (NPM1c) and others. We also discuss how altered condensate formation contributes to malignant transformation of hematopoietic cells, as described for promyelocytic leukemia protein (PML) in PML::RARA-driven acute promyelocytic leukemia (APL) and other myeloid malignancies. Finally, we discuss potential strategies for interfering with the molecular mechanisms related to AML-associated biomolecular condensates, as well as current limitations of the field.

Intrinsically Disordered Proteins; Phase-Separation; Cytoplasmic Nucleophosmin; Promyelocytic Leukemia; Transcription; Chromatin; Menin; P300; Pml; Nup98

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Lippincott Williams & Wilkins