HUMAN FLT3 FLK2 RECEPTOR TYROSINE KINASE IS EXPRESSED AT THE SURFACE OF NORMAL AND MALIGNANT HEMATOPOIETIC-CELLS/

FLT3/FLK2 is a receptor tyrosine kinase (RTK) which is thought to play an important role in early stages of hematopoiesis. Monoclonal antibo dies (mAbs) against the extracellular domain of human FLT3 were genera ted to study the cell surface expression of this class III RTK on norm al bone marrow cells and on leukemic blasts from patients with acute l eukemias. Functional analysis of five mAbs (SF1 series) revealed that all of them can mimic to variable extents the activity of the FLT3 lig and (FL) upon receptor activation and modulation, while only one mAb w eakly inhibited ligand binding. Using flow cytometry, we detected surf ace expression of FLT3 on cell lines of the myeloid (4/8) and B lympho id (7/10) lineages. On normal human hone marrow cells, the expression of FLT3 is restricted, in agreement with a presumed function of this r eceptor at the level of the stem cells and early committed progenitors . Expression of FLT3 was found on a fraction of CD34-positive and CD34 -negative cells. Three-color analysis further revealed that most of th e CD34(+++) FLT3(+) cells coexpress CD117 (KIT) at a high level. Final ly, FLT3 is expressed on leukemic blasts of 18/22 acute myeloid leukem ias (AML) and 3/5 acute lymphoid leukemias (ALL) of the B lineage, pro viding a possible application in diagnosis and therapy of these diseas es.