TUMOR-NECROSIS-FACTOR AND HUMAN ACUTE-LEUKEMIA

Tumor necrosis factor (TNF) is a major regulator of AML growth in vitr o and markedly enhances AML growth induced by GM-CSF/Il-3. TNF, on the other hand, suppresses the G-CSF stimulated AML cell proliferation an d serves as a modulator of growth factor receptors on AML cells. It up regulates GM-CSF and IL-3 receptors by a mechanism which depends on ne w protein synthesis and downregulates G-CSF receptors by activation of protein kinase C (PCK). The leukemic cells from patients with acute o r chronic leukemias have similar TNF receptor structures (MW 76 kD). S erum TNF levels increase in patients with both acute and chronic leuke mias especially in those with advanced disease. The clinical applicati on of TNF in association with GM-CSF or IL-3 may be of value for patie nts with AML.