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Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia

Author

Listed:
  • Feng Wang

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yunxuan Li

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Zhaona Yang

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Beijing Institute of Biological Products Company Limited
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Wenbin Cao

    (Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ying Liu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Luyao Zhao

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Tingting Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Chenxi Zhao

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jinmei Yu

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jiaojiao Yu

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jichao Zhou

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Xiaowei Zhang

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ping-Ping Li

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Mingzhe Han

    (Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Sizhou Feng

    (Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Billy Wai-Lung Ng

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Zhuo-Wei Hu

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Erlie Jiang

    (Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ke Li

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Bing Cui

    (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College
    Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College)

Abstract

Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph+ B-ALL cells secrete the chemokine CXCL16, which in turn promotes Th17 differentiation, attracts Th17 cells and forms a positive feedback loop supporting leukemia progression. These data demonstrate an involvement of Th17 cells in Ph+ B-ALL progression and suggest potential therapeutic options for Ph+ B-ALL with Th17-enriched niches.

Suggested Citation

  • Feng Wang & Yunxuan Li & Zhaona Yang & Wenbin Cao & Ying Liu & Luyao Zhao & Tingting Zhang & Chenxi Zhao & Jinmei Yu & Jiaojiao Yu & Jichao Zhou & Xiaowei Zhang & Ping-Ping Li & Mingzhe Han & Sizhou F, 2024. "Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44270-3
    DOI: 10.1038/s41467-023-44270-3
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    1. Roni Allaoui & Caroline Bergenfelz & Sofie Mohlin & Catharina Hagerling & Kiarash Salari & Zena Werb & Robin L. Anderson & Stephen P. Ethier & Karin Jirström & Sven Påhlman & Daniel Bexell & Balázs Ta, 2016. "Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    2. Younghun Jung & Jin Koo Kim & Yusuke Shiozawa & Jingcheng Wang & Anjali Mishra & Jeena Joseph & Janice E. Berry & Samantha McGee & Eunsohl Lee & Hongli Sun & Jianhua Wang & Taocong Jin & Honglai Zhang, 2013. "Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
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