Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.
Feng WangYunxuan LiZhaona YangWenbin CaoYing LiuLuyao ZhaoTingting ZhangChenxi ZhaoJin-Mei YuJiaojiao YuJichao ZhouXiao-Wei ZhangPing-Ping LiMingzhe HanSizhou FengBilly Wai-Lung NgZhuo-Wei HuErlie JiangKe LiBing CuiPublished in: Nature communications (2024)
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.
Keyphrases
- induced apoptosis
- acute lymphoblastic leukemia
- cell cycle arrest
- cell proliferation
- endoplasmic reticulum stress
- signaling pathway
- bone marrow
- oxidative stress
- acute myeloid leukemia
- gene expression
- pi k akt
- chronic myeloid leukemia
- inflammatory response
- regulatory t cells
- end stage renal disease
- dendritic cells
- newly diagnosed
- cell cycle
- big data
- electronic health record
- copy number
- binding protein
- nuclear factor
- allogeneic hematopoietic stem cell transplantation