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miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape

Author

Listed:
  • Fang Chen

    (City of Hope Medical Center and Beckman Research Institute)

  • Dandan Zhao

    (City of Hope Medical Center and Beckman Research Institute)

  • Yongfang Xu

    (City of Hope Medical Center and Beckman Research Institute)

  • Yi Zhang

    (City of Hope Medical Center and Beckman Research Institute
    Zhejiang University)

  • Min-Hsuan Chen

    (City of Hope Beckman Research Institute
    City of Hope Beckman Research Institute)

  • Khyatiben V. Pathak

    (Translational Genomics Research Institute
    Integrated Mass Spectrometry Shared Resource, City of Hope)

  • Nate Hansen

    (Translational Genomics Research Institute
    Integrated Mass Spectrometry Shared Resource, City of Hope)

  • Brooke Lovell

    (Translational Genomics Research Institute
    Integrated Mass Spectrometry Shared Resource, City of Hope)

  • Yong Liang

    (City of Hope Beckman Research Institute)

  • Katrina Estrella

    (City of Hope Medical Center and Beckman Research Institute)

  • Wei-Le Wang

    (City of Hope Beckman Research Institute)

  • Lucy Ghoda

    (City of Hope Medical Center and Beckman Research Institute)

  • Russell Rockne

    (City of Hope Beckman Research Institute)

  • Xiwei Wu

    (City of Hope Beckman Research Institute
    City of Hope Beckman Research Institute)

  • Haris Ali

    (City of Hope Medical Center and Beckman Research Institute)

  • Jianhua Yu

    (City of Hope National Medical Center)

  • Michael A. Caligiuri

    (City of Hope National Medical Center)

  • Stephen J. Forman

    (City of Hope National Medical Center)

  • Jeff M. Trent

    (Translational Genomics Research Institute)

  • Ya-Huei Kuo

    (City of Hope Medical Center and Beckman Research Institute)

  • Ling Li

    (City of Hope Medical Center and Beckman Research Institute)

  • Piotr Swiderski

    (City of Hope Beckman Research Institute)

  • Jianying Zhang

    (City of Hope Beckman Research Institute)

  • Marcin Kortylewski

    (City of Hope Beckman Research Institute)

  • Le Xuan Truong Nguyen

    (City of Hope Medical Center and Beckman Research Institute)

  • Patrick Pirrotte

    (Translational Genomics Research Institute
    Integrated Mass Spectrometry Shared Resource, City of Hope)

  • Mark Boldin

    (City of Hope Beckman Research Institute)

  • Guido Marcucci

    (City of Hope Medical Center and Beckman Research Institute
    City of Hope National Medical Center)

  • Bin Zhang

    (City of Hope Medical Center and Beckman Research Institute)

Abstract

We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells’ metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies.

Suggested Citation

  • Fang Chen & Dandan Zhao & Yongfang Xu & Yi Zhang & Min-Hsuan Chen & Khyatiben V. Pathak & Nate Hansen & Brooke Lovell & Yong Liang & Katrina Estrella & Wei-Le Wang & Lucy Ghoda & Russell Rockne & Xiwe, 2025. "miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56383-y
    DOI: 10.1038/s41467-025-56383-y
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    References listed on IDEAS

    as
    1. Nikolaos Patsoukis & Kankana Bardhan & Pranam Chatterjee & Duygu Sari & Bianling Liu & Lauren N. Bell & Edward D. Karoly & Gordon J. Freeman & Victoria Petkova & Pankaj Seth & Lequn Li & Vassiliki A. , 2015. "PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
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