Kinetic characteristics of de novo and secondary AML cells influence theirresponse to haemopoietic growth factor (HGF) priming and correlate with clinical outcome

This study has assessed the effect of in vitro haemopoietic growth factor ( HGF) priming on the S phase activity of cells from patients with de novo AM L and AML secondary to MDS. The occurrence of receptors for G-CSF, GM-CSF, IL-3 and SCF on marrow cells was assessed using immunofluorescent ligand bi nding assays. Additionally, patients responses to first phase induction che motherapy was recorded to examine whether in vitro kinetic data might corre late with clinical outcome. All kinetic and receptor assays were performed in normal marrow cells to ascertain their response to priming. Incubation o f AML cells in serum free medium (SFM) +/- G + GM-CSF, IL-3, SCF, G + GM-CS F + SCF or IL-3 + SCF prior to S phase assessment revealed that priming per mutations inclusive of SCF were most effective but also that the baseline l evel of S phase activity with SFM alone influenced the subsequent response to priming. Regardless of AML group, samples with low baseline S phase acti vity (<10%) were significantly more responsive than those with high (>10%) SFM S phase levels. However there was no corresponding difference in the pe rcentages of cells bearing receptors. In both AML groups, low baseline S ph ase activity was observed more frequently in samples from patients who achi eved CR. Normal samples possessed receptors for all HGFs and were responsiv e to all priming permutations except SCF alone. This study raises four poin ts: (a) it may be prudent to reserve the use of priming HGFs for those pati ents with low baseline S phase activity whose cells respond in vitro and to use SCF in these priming cocktails; (b) the presence of receptors capable of ligand binding in AML samples did not guarantee kinetic response; (c) no rmal progenitors were responsive to priming which may have implications for haemopoietic reconstitution post therapy; and (d) the kinetic characterist ics of AML progenitors may influence clinical outcome regardless of whether treatment includes HGFs. (C) 1999 Elsevier Science Ltd. All rights reserve d.