Kit Ligand (KitL) or Stem Cell Factor (SCF) and its receptor tyrosine kinase, c-Kit (CD117) are critical for the survival of germ cells, melanocytes, hematopoietic stem cells and mastocytes. Overexpression and gain-of-function mutations of c-kit were detected in several human cancers such as leukemia. Despite treatments with tyrosine kinase inhibitors (TKIs) notably, imatinib, tumor cells persist in the tissue microenvironment of the bone marrow in an integrin-dependent manner. These resident tumor cells can cause the development of therapy resistance due to secondary mutations in c-Kit and tumor relapse. So far, it is not understood why tumor cells are sensitive to TKI inhibitors when present in the blood, but escape this treatment when anchored to their niche in the bone marrow.