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

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 Feng, Billy Wai-Lung Ng, Zhuo-Wei Hu, Erlie Jiang (), Ke Li () and Bing Cui ()
Additional contact information
Feng Wang: Institute of Materia Medica, 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
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
Jiaojiao Yu: 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
Xiaowei Zhang: 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
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
Zhuo-Wei Hu: 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

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44270-3

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