Fig. 4

CXCR4/CXCL12 signaling in homing of hematopoietic stem cell (HSCs), CML leukemic stem cell (LSCs), and malignant B cells (i.e., CLL cells) to the bone marrow microenvironment. The perivascular niche is composed of a network of sinusoids (red) and adjacent reticular stromal cells niche (green) that constitutively secrete CXCL12. a In CML, LSCs (red cells) may exploit the same mechanism as HSCs (brown cells) to access niche. CXCR4/CXCL12-mediated interactions sheltered LSCs from the cytotoxic effects of TKIs. Interruption of CXCR4/CXCL12 interaction by AMD3100 may promote expulsion of quiescent LSCs from their niche and render them more accessible to targeted therapeutic agents. b In CLL, both HSCs and CLL cells express CXCL4, which directs chemotaxis of hematopoietic progenitor cells (HPC) and CLL from the circulation to the bone marrow. Malignant B cells (blue cells) utilize the CXCR4/CXCL12 axis to access niche that normally are restricted to HSC. This niche microenvironment will create favorable condition for their survival (such as fibronectin and hyaluronan) and provide survival, drug resistance signals to the CLL cells. Interruption of CXCR4/CXCL12 interaction by AMD3100 may promote expulsion of malignant B cells from bone marrow niche and render them more accessible to targeted therapeutic agents