Interleukin-27 remodels the bone marrow niche to suppress B-cell development and leukaemia progression in mouse models

  • EBioMedicine. 2026 May:127:106239. doi: 10.1016/j.ebiom.2026.106239.
Jian-Min Zhu  1 ,  Jing Xia  2 ,  Kai-Ming Chen  2 ,  Xue-Feng Bai  3 ,  Cai-Wen Duan  4
Affiliations
  • 1. Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. Electronic address: [email protected].
  • 2. Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • 3. Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, 518107, China. Electronic address: [email protected].
  • 4. Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. Electronic address: [email protected].
PMID: 41932204 DOI: 10.1016/j.ebiom.2026.106239
Abstract

Background: Interleukin-27 (IL-27) is an immunoregulatory cytokine, but its role in B-cell haematopoiesis and B-cell acute lymphoblastic leukaemia (B-ALL) within the bone marrow (BM) niche remains unclear.

Methods: IL-27 was delivered in vivo using adeno-associated virus. B-cell reconstitution, mixed BM chimeras, and an N-myc-driven B-ALL model were analysed by flow cytometry, transcriptional profiling, and survival studies. Group comparisons were assessed using Student's t-test, and survival was evaluated by Kaplan-Meier analysis with log-rank tests.

Findings: Sustained IL-27 expression selectively impaired B-cell reconstitution while preserving overall haematopoietic recovery, with marked reductions in CLPs and early B-cell subsets. IL-27 directly inhibited early B-lineage differentiation and concurrently remodelled the BM microenvironment by downregulating VCAM-1, ICAM-2, CXCL12, and IGF-1. These niche alterations were associated with reduced BM-resident B-ALL burden, enhanced chemotherapy efficacy, and improved survival in B-ALL-bearing mice. IL-27 showed no direct cytotoxicity toward B-ALL cells, supporting an indirect, niche-mediated mechanism.

Interpretation: IL-27 constrains B-cell haematopoiesis and B-ALL progression through coordinated progenitor inhibition and BM niche remodelling, revealing a cytokine-driven strategy with the potential to enhance leukaemia therapy.

Funding: This work was supported by the National Key R&D Program of China (Grant No. 2021YFA1100800 to A.-B.L.) and the National Natural Science Foundation of China (Grant No. 82100180).

Keywords
B-ALL; B-cell development; BM microenvironment; Haematopoiesis; IL-27.
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