Faculty, Staff and Student Publications

Publication Date

3-6-2025

Journal

Cell Stem Cell

DOI

10.1016/j.stem.2025.01.010

PMID

39954676

PMCID

PMC12097264

PubMedCentral® Posted Date

3-6-2026

PubMedCentral® Full Text Version

Post-print

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

Leukemia, Myeloid, Acute, Humans, Proto-Oncogene Proteins, Animals, Trans-Activators, Mice, Nuclear Proteins, RNA-Binding Proteins, Gene Expression Regulation, Leukemic, Cell Line, Tumor, Transcription, Genetic, Carcinogenesis, Cell Proliferation, Cell Differentiation

Published Open-Access

yes

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