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YBX1 expression and function in early hematopoiesis and leukemic cells

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Abstract

Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells along a particular lineage. Y-box protein (YBX1) is a transcription factor which is widely expressed throughout development and is involved in erythroid cell development; however, its role in early hematopoietic differentiation is not known. This study aims to investigate the role of YBX1 expression in early hematopoietic differentiation and leukemia. Here, we show that YBX1 is highly expressed in mouse erythroid myeloid lymphoid-clone 1 (EML), a hematopoietic precursor cell line, but is down-regulated in myeloid progenitors and GM-CSF-treated EML cells during the course of myeloid differentiation. Moreover, we found that lineage−/IL-7R−/c-kit+/Sca1+ (LKS; enriched fraction of hematopoietic stem cells) and lineage−/IL-7R−/c-kit+/Sca1− myeloid progenitor cells showed high level of YBX1 expression as compared to the differentiated cells like granulocytes in mouse bone marrow. Also, YBX1 protein was expressed at high levels in myeloid leukemic cell lines blocked at different stages of myeloid development. We further investigated the role of YBX1 in leukemic cells by knockdown studies and observed that down-regulation of YBX1 expression in K562 leukemic cells inhibited their proliferation ability, induced apoptosis, and differentiation towards megakaryocytic lineage upon arsenic trioxide treatments relative to untreated. Overall, our data indicates that YBX1 is down-regulated during myeloid differentiation and the aberrant YBX1 expression in leukemic cells could be a contributing factor in the development of leukemia by blocking their differentiation. Thus, YBX1 protein could be an excellent molecular target for therapy in myeloproliferative disorders and leukemia.

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Acknowledgements

We thank Dr. Schickwann Tsai for the generous gift of EML cell line used in this study. We also thank Dr. Thomas Iftner and Dr Johanna Schuetz for donating pSUPER YBX1 shRNA and pSUPER EV (Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany). We gratefully acknowledge the advice and constructive discussion of Dr. Sandeep Joshi. This work was supported in part by NIH NCRR COBRE (5P20RR020180) and WV-INBRE (5P20RR016477) grants which support the Marshall University Genomics Core Facility and the Marshall University Flow Cytometry Core Facility. This work was also supported by the NIH/NCI by R03CA129790.

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Jasjeet Bhullar & Vincent E. Sollars

  2. Department of Biochemistry and Microbiology, One John Marshall Drive (BBSC), Marshall University, Huntington, WV, 25755, USA

    Vincent E. Sollars

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  1. Jasjeet Bhullar
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  2. Vincent E. Sollars
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Correspondence to Vincent E. Sollars.

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Bhullar, J., Sollars, V.E. YBX1 expression and function in early hematopoiesis and leukemic cells. Immunogenetics 63, 337–350 (2011). https://doi.org/10.1007/s00251-011-0517-9

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  • DOI: https://doi.org/10.1007/s00251-011-0517-9

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