홍주영 (University of Texas Health Science Center at San Antonio) | 한빛사논문 > 한빛사

한빛사논문

조회174

University of Texas Health Science Center at San Antonio

Cell Stem Cell, Mar 06 2025, 32 (3) S1934-5909(25)00010-4 | https://doi.org/10.1016/j.stem.2025.01.010 PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1

Juyeong Hong ^{1 11}, Pinpin Sui ^{2 11}, 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 5}, Hongwei Zhou ⁶, Karina Hamamoto ⁷, Rui Su ⁸, C. Cameron Yin^{9 10}, Fengxi Ye ^{9 10}, Andrés E. Quesada ⁹, Jianjun Chen ⁸, Suming Huang ⁷, Daohong Zhou ^{3 5}, M. James You ^{9 10}, Feng-Chun Yang ^{2 5 *}, Jianlong Wang^{6 *}, Mingjiang Xu ^{1 5 12 *}

¹Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
²Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
³Department of Biochemistry & Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
⁴Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA
⁵Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
⁶Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia University Irving Medical Center, New York, NY 10032, USA
⁷Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
⁸Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA
⁹Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
¹⁰The University of Texas MD Anderson Cancer Center UT Health Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA
¹¹These authors contributed equally
¹²Lead contact

^*Corresponding authors: correspondence to Feng-Chun Yang, Jianlong Wang or Mingjiang Xu

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.

논문정보

형식Research article
게재일2025년 03월 (BRIC 등록일 2025-03-24)
연구진국외 연구진
분야 생명과학 > 노화/암생물학

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