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. 2025 Mar 6;32(3):463-478.e6.
doi: 10.1016/j.stem.2025.01.010. Epub 2025 Feb 14.

PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1

Juyeong Hong  1 , Pinpin Sui  2 , Ying Li  1 , Kerryn Y Xu  2 , Ji-Hoon Lee  1 , Juan Wang  1 , Shi Chen  1 , Peng Zhang  2 , Noah Wingate  1 , Asra Noor  2 , Yaxia Yuan  3 , Robert Hromas  4 , Hongwei Zhou  5 , Karina Hamamoto  6 , Rui Su  7 , C Cameron Yin  8 , Fengxi Ye  8 , Andrés E Quesada  9 , Jianjun Chen  7 , Suming Huang  6 , Daohong Zhou  10 , M James You  8 , Feng-Chun Yang  11 , Jianlong Wang  12 , Mingjiang Xu  13
Affiliations

PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1

Juyeong Hong et al. Cell Stem Cell. .

Abstract

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed and associated with poor survival in AML patients. Using human AML cells and mouse models, we demonstrate that PSPC1 is not required for normal hematopoiesis, but it is critical and essential for AML cells to maintain their leukemic characteristics. PSPC1 loss induces robust differentiation, suppresses proliferation, and abolishes leukemogenesis in diverse AML cells. Mechanistically, PSPC1 exerts a pro-leukemia effect by regulating a unique leukemic transcription program via cooperative chromatin binding with PU.1 and activation of tumor-promoting genes, including NDC1, which is not previously implicated in AML. Our findings uncover a unique and crucial role of PSPC1 dependency in AML and highlight its potential as a promising therapeutic target for AML.

Keywords: AML; NDC1; PSPC1; PU.1; hematopoiesis; leukemia.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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