Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia:PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts

We investigated effects of Platelet-derived growth factor (PDGF) and Platel et factor 4 (PF-4) on the functional characteristics of native, human acute myelogenous leukemia (AML) blasts. AML blast expression of the PDGF-recept or a-chain was detected for a subset of patients (45%), whereas PDGF-recept or P-chain expression was detected for most patients (90%). Constitutive AM L blast release of the PDGF-AB isoform (the major form also derived from no rmal platelets) was detected for 43% of patients, whereas PDGF-BB release w as not detected for any patient. The PDGF isoforms AA, AB and BB had dose-d ependent and divergent effects on spontaneous and cytokine-dependent AML bl ast proliferation, whereas for constitutive cytokine secretion (IL-1 beta, IL-6, TNF-alpha) inhibitory effects were rare, and all three isoforms usual ly had no effect or enhanced the constitutive secretion. The PDGF effects w ere caused by a direct effect on the AML blasts and were not dependent on t he presence of serum. The PDGF effects could also be detected after in vitr o culture of AML cells in the presence of IL-4+granulocyte-macrophage colon y stimulating factor. PF-4 had divergent effects on proliferation and cytok ine secretion by native AML blasts. Our results suggest that exogenous (e.g . platelet-secreted) PDGF and PF-4 can function as regulators of leukemic h ematopoiesis and possibly also modulate the function of residual AML cells in peripheral blood stem cell grafts. On the other hand, endogenous release of PDGF-AB by native blasts may modulate the function of normal cells in t he bone marrow microenvironment (e.g. bone marrow stromal cells).