ArticleBlood2021
The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Modulation of the bone marrow microenvironment by acute B-cell lymphoblastic leukemia-derived large oncosomes.Blood advances · 2026Article
- Pharmacological inhibition of sclerostin protects bone from B-cell acute lymphoblastic leukemia-mediated destruction.HemaSphere · 2026Article
- Cytokines, Signaling and Epigenetic Mechanisms: Shaping the Acute Lymphoblastic Leukemia Microenvironment.Cells · 2026Review
- Microbial metabolite oxindole curbs acute lung injury by suppressing CXCL13.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Stem-like T cells: molecular regulation, functional diversity, and therapeutic implications across diseases.Journal of translational medicine · 2025Review
- NIPA1 depletion in tumor-associated macrophages via IGFBP2/EGFR attenuates acute myeloid leukemia progression and chemoresistance.Annals of hematology · 2025Article
- Review
- The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential.Frontiers in immunology · 2025Review
- CXCL13-neutralizing Antibody Alleviate Chronic Skeletal Muscle Degeneration in a Mouse Model.Current molecular medicine · 2025Article
- The utility of CXCL13 and circulating CXCR5Frontiers in immunology · 2025Article
- Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting.Nature communications · 2024Article
- Spatially Resolved Tumor Microenvironment Predicts Treatment Outcomes in Relapsed/Refractory Hodgkin Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Distinct and targetable role of calcium-sensing receptor in leukaemia.Nature communications · 2023Article
- Review
- Flow cytometric assessment of leukemia-associated monocytes in childhood B-cell acute lymphoblastic leukemia outcome.Blood advances · 2023Article
- Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression.Blood advances · 2023Article
- Prognostic value of cross-lineage expression of the myeloid-associated antigens CD13 and CD33 in adult B-lymphoblastic leukemia: A large real-world study of 1005 patients.Cancer medicine · 2023Article
- The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia.Frontiers in oncology · 2023Review
- The Role of CXC Chemokines in Cancer Progression.Cancers · 2022Review
- Changes in the Expression and Functional Activities of C-X-C Motif Chemokine Ligand 13 (International journal of molecular sciences · 2022Article
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Authors and funding
25 authors at 12 institutions in 4 countries.
Funding
Abstract
B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, whereas chronic myeloid leukemia is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young vs old mice, we recapitulated B-ALL preponderance in children vs adults. We showed differential effects of young vs old BM macrophages on B-ALL cell function. Molecular profiling using RNA- and ATAC-sequencing revealed pronounced differences in young vs old BMM-derived macrophages and enrichment for gene sets associated with inflammation. In concordance with the role of C-X-C motif chemokine (CXCL) 13 for disease-associated B-cell chemoattraction, we found CXCL13 to be highly expressed in young macrophages on a translational compared with a transcriptional level. Inhibition of CXCL13 in BM macrophages impaired leukemia cell migration and decreased the proliferation of cocultured B-ALL cells, whereas recombinant CXCL13 increased pAKT and B-ALL cell expansion. Pretreatment of B-ALL-initiating cells with CXCL13 accelerated B-ALL progression. Deficiency of Cxcr5, the receptor for CXCL13, on B-ALL-initiating cells prolonged murine survival, whereas high expression of CXCR5 in pediatric B-ALL may predict central nervous system relapse. CXCL13 staining was increased in bone sections from pediatric compared with adult patients with B-ALL. Taken together, our study shows that the age of the BMM and, in particular, BM macrophages influence the leukemia phenotype. The CXCR5-CXCL13 axis may act as prognostic marker and an attractive novel target for the treatment of B-ALL.
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