Breaking the CXCR4/CXCL12 signaling during blood stem cell release caused by GCSF or cyclophosphamide

Mobilization of hematopoietic progenitor cells (HPCs) by GCSF is associated with the cleavage of the CXCR4 receptor on these cells.

• Cleavage of CXCR4 on HPCs leads to a loss of their ability to respond to the chemokine SDF-1.
• Concentrations of SDF-1 in the bone marrow decrease during the mobilization of HPCs.
• This decrease in SDF-1 coincides with the accumulation of serine proteases that can cleave and inactivate SDF-1.
• Both SDF-1 and CXCR4 are crucial for the retention of HPCs in the bone marrow.
• The degradation of SDF-1 and CXCR4 may be a key factor in the process of HPC mobilization into peripheral blood.

Simplified