Reduced colony‐stimulating factor 1 receptor expression in myeloid cells has limited impact on chronic lymphocytic leukaemia progression

British Journal of Haematology, vol. 209, pp. 939–952

Abstract

Targeting the colony-stimulating factor 1 receptor (CSF1R) to remove tumour-associated macrophages is being explored as cancer therapy. This strategy may be relevant for chronic lymphocytic leukaemia (CLL), which strongly depends on support from myeloid cells. However, it is unclear how CSF1R expression affects the CLL microenvironment and leukaemic progression. To examine this question, we created Eμ-TCL1 transgenic mice for CLL with Csf1r haploinsufficiency to investigate changes in myeloid cells, Csf1r expression and leukaemia progression. Csf1r haploinsufficiency reduced Csf1r expression on circulating monocytes, but did not significantly impair its expression in tissue macrophages or change the overall numbers of monocytes or macrophages in blood and lymphoid tissues. Eμ-TCL1 transgenic mice with lower Csf1r levels had less leukaemia during early disease, but this effect faded with disease progression, and their overall survival was similar to controls. Furthermore, in vitro co-culture demonstrates that depletion of CSF1R expression on cell lines did not affect the survival or migration of patient-derived CLL cells. In summary, our results show that while the CSF1R pathway is important for maintaining the myeloid cells that support CLL, simply reducing CSF1R expression has only a limited effect on disease progression. Attempts to target the CSF1R for leukaemic therapy might benefit from a stronger depletion of macrophages or the combination with other agents.

Authors 14

1. Natascha Rosen

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

2. Guillermo Rodríguez‐Real

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

3. Alexander F. vom Stein

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

4. Luca D Schreurs

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

5. Trong-Hieu Nguyen Aachen Institute of Molecular Medicine

   RWTH Aachen University · University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

   Institute of Molecular Medicine RWTH Aachen University Aachen Germany

6. Viktoria Kohlhas

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

7. Thanh Tung Truong

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

8. Sebastian Reinartz

   University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

   Affiliation as printed

   Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

9. Sumiya Iqbal

   University of Cologne

   Affiliation as printed

   Center for Molecular Medicine Cologne Cologne Germany

   Institute of Inorganic and Materials Chemistry University of Cologne Cologne Germany

10. Shaista Ilyas

    University of Cologne

    Affiliation as printed

    Center for Molecular Medicine Cologne Cologne Germany

    Institute of Inorganic and Materials Chemistry University of Cologne Cologne Germany

11. Sanjay Mathur

    University of Cologne

    Affiliation as printed

    Center for Molecular Medicine Cologne Cologne Germany

    Institute of Inorganic and Materials Chemistry University of Cologne Cologne Germany

12. Nina Reinart

    University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

    Affiliation as printed

    Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

13. Phuong‐Hien Nguyen corresponding

    University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

    Affiliation as printed

    Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany

14. Michael J. Hallek corresponding

    University of Cologne · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · University Hospital Cologne

    Affiliation as printed

    Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging‐Associated Diseases University of Cologne Cologne Germany