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. 2023 Aug;118(2):277-287.
doi: 10.1007/s12185-023-03612-z. Epub 2023 May 13.

The Nup98::Nsd1 fusion gene induces CD123 expression in 32D cells

Kenji Okamoto  1 , Toshihiko Imamura  2 , Seiji Tanaka  1 , Takayo Urata  1 , Hideki Yoshida  1 , Norio Shiba  3 , Tomoko Iehara  1
Affiliations

The Nup98::Nsd1 fusion gene induces CD123 expression in 32D cells

Kenji Okamoto et al. Int J Hematol. 2023 Aug.

Abstract

The NUP98::NSD1 fusion gene is associated with extremely poor prognosis in patients with acute myeloid leukemia (AML). NUP98::NSD1 induces self-renewal and blocks differentiation of hematopoietic stem cells, leading to development of leukemia. Despite its association with poor prognosis, targeted therapy for NUP98::NSD1-positive AML is lacking, as the details of NUP98::NSD1 function are unknown. Here, we generated 32D cells (a murine interleukin-3 (IL-3)-dependent myeloid progenitor cell line) expressing mouse Nup98::Nsd1 to explore the function of NUP98::NSD1 in AML, including comprehensive gene expression analysis. We identified two properties of Nup98::Nsd1 + 32D cells in vitro. First, Nup98::Nsd1 promoted blocking of AML cell differentiation, consistent with a previous report. Second, Nup98::Nsd1 increased dependence on IL-3 for cell proliferation, due to overexpression of the alpha subunit of the IL-3 receptor (IL3-RA, also known as CD123). Consistent with our in vitro data, IL3-RA was also upregulated in samples from patients with NUP98::NSD1-positive AML. These results highlight CD123 as a potential new therapeutic target in NUP98::NSD1-positive AML.

Keywords: Acute myeloid leukemia; Alpha subunit of the IL-3 receptor; CD123; NSD1; NUP98.

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