EXPRESSION OF TYPE-III RECEPTOR TYROSINE KINASES FLT3 AND KIT AND RESPONSES TO THEIR LIGANDS BY ACUTE MYELOID-LEUKEMIA BLASTS

The stem cell tyrosine kinase 1 (STK1) protein is the human homologue of the murine FLT3 gene product, a receptor belonging to the FMS/KIT f amily. FLT3 and KIT with their ligands control the growth and differen tiation of early human hemopoietic cells. In the present study, 16 cas es of acute myeloid leukemia (AML) were examined by flow cytometry for cell surface expression of FLT3 and KIT receptors. All cases were als o tested for their proliferative response to human FLT3 ligand (FL) an d KIT ligand (KL) and for colony formation in the presence of single o r associated cytokines. Among 16 AML cases tested, 10/16 expressed FLT 3 receptor and 12/16 expressed KIT receptor, without any correlation w ith FAB subtype. FL and KL stimulated the proliferation of leukemic bl asts in 11/16 AML cases (including five FLT3 or KIT receptor-negative cases), with an additive effect when added simultaneously, By contrast , some receptor-expressing AMLs did not display significant proliferat ive responses to their respective ligands. FL and KL as single factors induced or significantly increased the colony formation by clonogenic precursor cells respectively in eight and six of 13 cases tested. In some cases growth factor association significantly enhanced colony gro wth. Taken together these observations provide evidence that the patte rn of FLT3 and KIT receptor expression is extremely Variable among the AMLs and that receptor presence is not necessarily combined with prol iferative and clonogenic response or vice versa.