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STK10 mutations block erythropoiesis in acquired pure red cell aplasia via impairing ribosome biogenesis

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Abstract

Acquired pure red cell aplasia (PRCA) is anemia associated with the absence of erythroblasts and is characterized by persistent and easy recurrence. However, the underlying mechanisms of acquired PRCA remain obscure, and the role of gene mutations in the pathogenesis of acquired PRCA is not fully characterized. In the present study, we detected thirty newly diagnosed patients with acquired PRCA using whole exome sequencing, and a potential role for STK10 in acquired PRCA was uncovered. The mRNA levels of STK10 in three patients with STK10 mutations were decreased. These three patients had a poor response to immunosuppressive therapy and two died in the follow-up period. Here we report that knockdown of STK10 inhibits erythroid differentiation and promotes apoptosis of K562 cells. We show that knockdown of STK10 resulted in inhibition of ribosome biogenesis and reduced ribosome levels in K562 cells. We also show that the p53 signaling pathway is activated by knockdown of STK10. Our results imply that ribosome biogenesis downregulation together with pathological p53 activation prevents normal erythropoiesis. Our study uncovers a new pathophysiological mechanism leading to acquired PRCA driven by STK10 mutations.

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No datasets were generated or analysed during the current study.

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Acknowledgements

We thank all patients who consented to disclose their medical records and answered our review calls. Their cooperation and helpful comments throw light upon our data collection and statistical analysis.

Funding

This study was supported by grants from National Natural Science Foundation of China (81900118), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2016-I2M-3-004), National Key Research and Development Program of China (2016YFC0901500), Clinical Science Foundation of Anhui Medical University (2021XKJ160) and Research Project of Integrated Traditional Chinese and Western Medicine of Tianjin Health Commission (2023078).

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Authors and Affiliations

  1. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Jichun Yang, Xinrui Qiao & Xun Zhou

  2. Department of Hematology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, China

    Xiaofeng Shi

  3. Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Xinyao Liu & Zhangbiao Long

  4. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, China

    Hongmin Li, Yali Du, Miao Chen, Bing Han & Zhangbiao Long

  5. Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Dongdong Fang

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  1. Jichun Yang
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Contributions

Z.L., J.Y., and B.H. designed the study, Z.L., J.Y., X.S., X.L., X.Q., X.Z., Y.D., H.L. and D.F. performed the experiments and analyzed the data, M.C. collected samples, Z.L. J.Y. and X.S. wrote the manuscript. All authors reviewed the manuscript and approved the final version of the manuscript.

Corresponding authors

Correspondence to Bing Han or Zhangbiao Long.

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This study was approved by the Peking union medical college hospital ethics committee and was performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all patients for being included in the study.

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The authors declare no competing interests.

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Yang, J., Shi, X., Liu, X. et al. STK10 mutations block erythropoiesis in acquired pure red cell aplasia via impairing ribosome biogenesis. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05802-z

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