EXPRESSION AND REGULATION OF C-KIT RECEPTOR AND RESPONSE TO STEM-CELLFACTOR IN CHILDHOOD MALIGNANT T-LYMPHOBLASTIC CELLS

The cytokine stem cell factor (SCF) synergizes with IL-7 to enhance th e proliferation of thymocytes. We therefore investigated the role of t he SCF receptor, the protooncogene c-kit, in the pathogenesis of pedia tric T-lineage malignancies. Expression and regulation of c-kit in cel ls from children with non-Hodgkin's lymphoma (T-NHL) or acute lymphobl astic leukemia (T-ALL) and the proliferative effect of SCF on these ce lls were examined in seven cell lines and 21 biopsy tumor cell prepara tions. Inducibility of c-kit receptors by SCF, IL-1 beta, IL-2, IL-7, TGF-beta, TNF-alpha, PMA or calcium ionophore A23187 was studied by fl ow cytometry (FCM). C-kit receptors were detected in three out of seve n T-lymphoblastic cell lines and in nine out of 21 biopsy tumor cell p reparations. Upregulation of c-kit could be induced by cultivation, an d to a higher extent by cultivation and addition of IL-1 beta, TNF-alp ha, TGF-beta or A23187. Down-regulation of c-kit occurred in the prese nce of SCF or PMA. SCF caused a downregulation of c-kit receptors in e ight of nine, and a proliferative response in three of 11 c-kit-positi ve T-lymphoblastic cell preparations. We conclude that c-kit is able t o transduce a growth stimulatory signal in some T-lymphoblastic cells and that its expression may not be detectable in a resting metabolic o r proliferative state.