Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance.
- Resource Type
- Academic Journal
- Authors
- Bührer ED; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.; Amrein MA; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.; Forster S; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.; Isringhausen S; Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland.; Schürch CM; Institute of Pathology, University of Bern, Bern, Switzerland.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.; Bhate SS; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Brodie T; Visceral Surgery, Department of BioMedical Research, University of Bern, Bern, Switzerland.; Zindel J; Visceral Surgery, Department of BioMedical Research, University of Bern, Bern, Switzerland.; Stroka D; Visceral Surgery, Department of BioMedical Research, University of Bern, Bern, Switzerland.; Sayed MA; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Nombela-Arrieta C; Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland.; Radpour R; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Riether C; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland.; Ochsenbein AF; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. adrian.ochsenbein@insel.ch.; Tumor Immunology, Department for BioMedical Research, University of Bern, Bern, Switzerland. adrian.ochsenbein@insel.ch.
- Source
- Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE
- Subject
- Language
- English
Disease progression and relapse of chronic myeloid leukemia (CML) are caused by therapy resistant leukemia stem cells (LSCs), and cure relies on their eradication. The microenvironment in the bone marrow (BM) is known to contribute to LSC maintenance and resistance. Although leukemic infiltration of the spleen is a hallmark of CML, it is unknown whether spleen cells form a niche that maintains LSCs. Here, we demonstrate that LSCs preferentially accumulate in the spleen and contribute to disease progression. Spleen LSCs were located in the red pulp close to red pulp macrophages (RPM) in CML patients and in a murine CML model. Pharmacologic and genetic depletion of RPM reduced LSCs and decreased their cell cycling activity in the spleen. Gene expression analysis revealed enriched stemness and decreased myeloid lineage differentiation in spleen leukemic stem and progenitor cells (LSPCs). These results demonstrate that splenic RPM form a niche that maintains CML LSCs in a quiescent state, resulting in disease progression and resistance to therapy.
(© 2022. The Author(s).)