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UTX is an escape from X-inactivation tumor-suppressor in B cell lymphoma

Author

Listed:
  • Xiaoxi Li

    (University of Chinese Academy of Sciences
    Jiangsu University)

  • Yanli Zhang

    (University of Chinese Academy of Sciences)

  • Liting Zheng

    (University of Chinese Academy of Sciences)

  • Mingxian Liu

    (University of Chinese Academy of Sciences)

  • Charlie Degui Chen

    (University of Chinese Academy of Sciences)

  • Hai Jiang

    (University of Chinese Academy of Sciences)

Abstract

To explain the excess cancer rate in males, several candidates for “escape from X-inactivation tumor-suppressor” (EXITS) were recently identified. In this report we provide direct experimental evidence supporting UTX’s role as an EXITS gene. Using a mouse lymphoma model, we show clear dosage effect of UTX copy number during tumorigenesis, which strongly supports the EXITS theory. Importantly, UTX deletion not only accelerates lymphomagenesis, it also strongly promotes tumor progression. UTX-knockout tumors are more aggressive, showing enhanced brain dissemination and formation of blood vessels. Efnb1 is overexpressed in UTX KO tumors and can lead to such phenotypes. In human patients, lymphomas with low UTX expression also express high levels of Efnb1, and cause significantly poor survival. Lastly, we show that UTX deficiency renders lymphoma sensitive to cytarabine treatment. Taken together, these data highlight UTX loss’s profound impacts on tumor initiation and drug response.

Suggested Citation

  • Xiaoxi Li & Yanli Zhang & Liting Zheng & Mingxian Liu & Charlie Degui Chen & Hai Jiang, 2018. "UTX is an escape from X-inactivation tumor-suppressor in B cell lymphoma," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05084-w
    DOI: 10.1038/s41467-018-05084-w
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    Cited by:

    1. Omar F Iskanderani, 2018. "Substantial Dynamics of Lymphomatous Transformation from Low-Grade to High-Grade Performance," Cancer Therapy & Oncology International Journal, Juniper Publishers Inc., vol. 11(5), pages 34-37, September.

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