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Transcriptional control and signal transduction, cell cycle

Nucleolin promotes execution of the hematopoietic stem cell gene expression program

Leukemia volume 32, pages 1865–1868 (2018)Cite this article

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Nucleolin is a multifunctional protein of growing and cancer cells, and serves as a candidate molecular target for cancer therapy (reviewed in refs. [1,2,3]). Nucleolin is directly involved in regulation of gene transcription and RNA metabolism, and also in DNA damage repair and cell-surface signaling [1,2,3,4,5]. It is preferentially expressed in hematopoietic stem/progenitor cells (HSPCs), as opposed to differentiated hematopoietic tissue, while its aberrant activity is associated with certain hematological malignancies [1, 3, 6] (and references in [1, 3, 6, 7]). Nucleolin activates CD34 and AC133/CD133 expression through defined mechanisms, and promotes long-term, cytokine-dependent maintenance of HSPCs [6, 7]. Working out the relationship of nucleolin to stem cell gene expression in hematopoiesis will improve understanding of hematopoietic stem/progenitor cells at the molecular level.

This study describes that, in human HSPCs, nucleolin promotes execution of gene expression programs of hematopoietic stem cells (HSCs) and stemness shared by HSCs and AML LSCs. Furthermore, nucleolin affects transcription factor activity and upregulates a number of HSC-enriched transcriptional regulators, including homeobox A9 (HOXA9) and the ETS transcription factor ERG. Thus, nucleolin drives an expression program that involves HOXA9 and ERG. The study provides new insights into molecular networks relevant to stem/progenitor cells in normal and malignant hematopoiesis.

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Acknowledgements

The work was funded, PI E. Grinstein, by Deutsche Forschungsgemeinschaft, grant GR 3581/2-1, and José Carreras Leukämie-Stiftung, grant DJCLS R 12/32.

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Authors and Affiliations

  1. Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

    Csaba Mahotka

  2. Institute of Pathology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

    Sanil Bhatia & Edgar Grinstein

  3. Bioinformatics, Miltenyi Biotec GmbH, Bergisch Gladbach, Germany

    Jutta Kollet

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  1. Csaba Mahotka
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  2. Sanil Bhatia
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  4. Edgar Grinstein
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Correspondence to Edgar Grinstein.

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Mahotka, C., Bhatia, S., Kollet, J. et al. Nucleolin promotes execution of the hematopoietic stem cell gene expression program. Leukemia 32, 1865–1868 (2018). https://doi.org/10.1038/s41375-018-0090-4

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