Reduced colony-stimulating factor 1 receptor expression in myeloid cells has limited impact on chronic lymphocytic...

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.