The Flt gene family of receptor tyrosine kinases includes Flt-1, KDR/Flk-1, Flt-3, and Flt-4. They encode receptors for VEGF, characterized by seven Ig-loops within their extracellular domain and a split kinase domain within the cytoplasmic domain. VEGF is an important angiogenic factor of many solid tumors and is also involved in the differentiation of endothelial cells. Flt-1 (Fms-like tyrosine kinase, VEGF-R1) is expressed on endothelial cells and on the common precursors of endothelial and hematopoietic stem cells. KDR (Flk-1, VEGF-R2) is the principal receptor involved in VEGF signaling. KDR is expressed on endothelial cells and stimulates angiogenesis, but is also expressed on bone marrow cells, and is thought to play a role in driving the proliferation of most or all leukemic cells. Flt3 (also known as Flk-2) is a class III receptor tyrosine kinase that is closely related to c-Kit and c-Fms. It is expressed in primitive hematopoietic cells and its ligand exerts proliferative effects on these cells in co-operation with other cytokines.