Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38172124.
- Also identified by DOI 10.1038/s41467-023-44270-3 and PMC identifier 10764960.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph<sup>+</sup> B-ALL patients. IL-17A promotes the progression of Ph<sup>+</sup> B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph<sup>+</sup> B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph<sup>+</sup> 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<sup>+</sup> B-ALL progression and suggest potential therapeutic options for Ph<sup>+</sup> B-ALL with Th17-enriched niches.
Medical subject headings
- Philadelphia Chromosome
- Precursor Cell Lymphoblastic Leukemia-Lymphoma