EXPRESSION OF FLT4 AND ITS LIGAND VEGF-C IN ACUTE MYELOID-LEUKEMIA

FLT4 represents a recently cloned member of class III receptor tyrosin e kinases which include receptors for the angiogenic growth factor VEG F, namely FLT1 and KDR. The ligand of FLT4 has been identified as VEGF -C which shares sequence homology with VEGF and P1GF. In the adult FLT 4 shows a restricted expression pattern that is limited to lymphatic e ndothelia and endothelia of some high endothelial venules (HEV). FLT4 has also been detected in some tumor cell lines including the hematopo ietic line HEL. We therefore investigated expression of FLT4 and its l igand VEGF-C in fresh samples from patients with AML. Using a sensitiv e PCR method we detected FLT4 m-RNA in 15 of 41 patients with de novo AML at diagnosis or relapse and in three of 12 patients with secondary AML. FLT4 expression was confirmed by immunocytochemistry in a subgro up of the studied patient population. FLT4 was also found in leukemic cell line U937, but not TF-1 and KG1a. VEGF-C expression was found in leukemic samples of four of seven FLT4-positive and four of six FLT4-n egative patients. U937 cells also produced VEGF-C m-RNA. Interestingly , FLT4 expression was not detected in bone marrow samples of 15 normal volunteer donors or in CD34-positive cells from three additional dono rs. Possible autocrine and paracrine growth stimulation of leukemic bl asts by VEGF-C is currently being investigated in our laboratory.