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Effect of knockdown of Nol10 on gene expression in murine leukemia cells expressing NUP98::DDX10

ABSTRACT: NUP98 rearrangements associated with acute myeloid leukemia and myelodysplastic syndromes generate NUP98-fusion proteins. One such fusion protein, NUP98::DDX10, contains the putative RNA helicase DDX10. The molecular mechanism by which NUP98::DDX10 induces leukemia is not well understood. Here, we show that 24 amino acids within the DDX10 moiety of NUP98::DDX10 are crucial for cell immortalization and leukemogenesis. NOL10, nucleolar protein 10, interacts with the 24 amino acids, and NOL10 is a critical dependency of NUP98::DDX10 leukemia development. Studies in a mouse model of NUP98::DDX10 leukemia showed that loss of Nol10 impaired disease progression and improved survival. We also identified a novel function of NOL10 in that it acts cooperatively with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA. Collectively, these findings suggest that NOL10 is a critical regulator of NUP98::DDX10 leukemia, and that targeting NOL10 (or the serine synthesis pathway regulated by NOL10) may be an effective therapeutic approach.

ORGANISM(S): Mus musculus

PROVIDER: GSE279389 | GEO | 2025/03/31

REPOSITORIES: GEO

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