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Acute lymphoblastic leukemia

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

Leukemia volume 31, pages 1079–1086 (2017)Cite this article

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Abstract

The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

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Acknowledgements

We thank M Greaves for critical comments on the paper. We thank B Zhang for the provision of fev:GFP zebrafish. B Zhao and C Duan are also acknowledged for their technical assistance in flow-sorting and mouse injection, respectively. This work was supported by grants from the National Basic Research Program of China (Grant No. 2012CB967001 to D-LH and 2010CB945300 and 2011CB943900 to FL) and the National Natural Science Foundation of China (Grant Nos. 81120108006, 90919055 and 91442106 to D-LH and 31425016 to FL).

Author contributions

T-HL designed and performed the experiments and analyzed the results; Y-JT and T-HL collected and analyzed the clinical data; LW and FL performed zebrafish experiments; YH and Q-JY collected human fetal liver and BM cells; X-LG, YZ, LC, HZ, XL and L-HZ collected human CB cells; J-YT, B-SL, J-QM and L-GL collected patient samples and related clinical information; AF detected FEV expression and analyzed data; TE, FL and G-QC discussed the data and contributed to the writing of the manuscript; D-LH supervised the project, designed the experiments and wrote the paper.

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Author notes

  1. T-H Liu, Y-J Tang, Y Huang and L Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathophysiology and Ruijin Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China

    T-H Liu, Y Huang, X-L Guo, Q-J Ye, G-Q Chen & D-L Hong

  2. Department of Hematology and Oncology, Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Shanghai Children’s Medical Center, SJTU-SM, Shanghai, China

    Y-J Tang, B-S Li & J-Y Tang

  3. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    L Wang & F Liu

  4. Shanghai Institute of Hematology, Ruijin Hospital, SJTU-SM, Shanghai, China

    J-Q Mi

  5. Hematological Department, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China

    L-G Liu

  6. Shanghai Cord Blood Bank, Shanghai, China

    H Zhu, Y Zhang & L Chen

  7. Huangshi Love Health Hospital, Huangshi, China

    X Liu & L-H Zhang

  8. Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK

    A Ford

  9. Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK

    T Enver

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  1. T-H Liu
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Correspondence to F Liu, G-Q Chen or D-L Hong.

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Liu, TH., Tang, YJ., Huang, Y. et al. Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin. Leukemia 31, 1079–1086 (2017). https://doi.org/10.1038/leu.2016.313

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