FLT3 RECEPTOR EXPRESSION ON THE SURFACE OF NORMAL AND MALIGNANT HUMANHEMATOPOIETIC-CELLS

FLT3 ligand is a hematopoietic growth factor that plays a key role in growth of primitive hematopoietic cells. FLT3 receptor mRNA is found i n early hematopoietic progenitors and in human myeloid leukemia blasts . Much less is known about the surface expression of FLT3 receptor on human hematopoietic cells. Using human(125)I-FLT3 ligand, we have iden tified and characterized surface FLT3 receptors on normal and malignan t human hematopoietic cells and cell lines. Our results showed that su rface display of FLT3 receptor was greatest in fresh myeloid leukemia blast cells and myeloid leukemia cell lines. Erythroleukemic and megak aryocytic leukemia cell lines (n = 5) bound little to no I-125-FLT3 li gand. Scatchard analysis of I-125-FLT3 ligand binding data shows that three myeloid leukemia cell lines, ML-1, AML-193, and HL-60, as well a s normal human marrow mononuclear cells, exhibit high affinity FLT3 re ceptors. Crosslinking of I-125-FLT3 ligand to FLT3 receptors on the su rface of ML-1 myeloid leukemia cells indicates that the FLT3 receptor forms homodimers in the presence of FLT3 ligand. The rates of FLT3 lig and internalization and degradation were determined by binding I-125-F LT3 ligand to ML-1 cells and acid stripping to distinguish surface bou nd from internalized ligand. Internalized I-125-FLT3 ligand was detect ed within 5 minutes after binding to ML-1 cells. In addition, we evalu ated the effect of FLT3 ligand on megakaryocytic colony growth and nuc lear endoreduplication, alone or in the presence of thrombopoietin. FL T3 ligand did not promote colony forming unit megakaryocyte (CFU-Meg) colony growth or megakaryocyte nuclear maturation, nor did FLT3 ligand augment the effects of thrombopoietin on these measures of megakaryop oiesis. These data indicate that the FLT3 receptor shares several char acteristics with the c-kit receptor including dimerization and rapid i nternalization. However, the more restricted cellular distribution of the FLT3 receptor may target the effects of FLT3 ligand to primitive h ematopoietic cells and to myeloid and lymphoid progenitor cells, in co ntrast to the pleiotropic effects of the c-kit receptor ligand, stem c ell factor. (C) 1996 by The American Society of Hematology.