Receptor ligation and mutations of growth factor receptor tyrosine kinases: Proliferation of primary AML cells is increased by receptor ligation [103]; receptor tyrosine kinase (RTK) mutations (e.g., c-kit mutations, FLT3-mutations) can cause constitutive signaling [98]. High CXCR4 levels is seen for a minority of patients and is associated with adverse prognosis [105]. Here, FLT3 is linked to acute myeloid leukemia.