STEM-CELL FACTOR AND PIXY-321 IN ACUTE LYMPHOBLASTIC-LEUKEMIA - IN-VITRO STUDY ON PROLIFERATIVE EFFECTS AND APOPTOSIS

Management of acute lymphoblastic leukemia (ALL) patients may include growth factors (GFs) to reduce post-chemotherapy aplasia. A potential risk of GF administration is a stimulatory signal on the leukemic popu lation. In the present study we investigated the proliferative and pro grammed cell death (PCD) effect of two cytokines that have recently en tered clinical use, stem cell factor (SCF) and the granulocyte colony stimulating factor/IL-3 fusion molecule (PIXY-321), on 14 ALL samples. The activity of IL-7, a cytokine involved in the regulation of ALL ce ll proliferation, was also tested alone and in combination with these two cytokines. Using the acridine orange flow cytometric technique and the clonogenic assay, we showed that none of these cytokines was capa ble of significantly increasing the mean percentage of S-phase cells a nd CFU-L number. A mean decrease of G(0) cells from 60.6% to 52.6% (p = 0.02), coupled by a significant increase of G(1) cells from 28.2% to 37.9% (p = 0.003) was demonstrated in the presence of PIXY-321. IL-7 alone and in combination with either PIXY-321 or SCF induced similar c hanges in the percentage of cells in G(0) and G(1). SCF showed no acti vity on G(0) depletion. When each individual sample was analyzed separ ately, some heterogeneity was observed. An increase of S phase was rec orded in a proportion of cases after SCF and PIXY-321 exposure. Howeve r, none of the cytokines evaluated by a clonogenic assay following liq uid culture was capable of maintaining or promoting self-renewal of le ukemic precursors, as determined by plating fresh cells at time 0. Det ection of cytokine effects on apoptosis showed that SCF and PIXY-321 d id not significantly reduce the mean percentage of cells in PCD, where as a significant protective effect was observed in the presence of IL- 7 (p = 0.02). We conclude that PIXY-321 and, to a further extent, SCF fail to induce leukemic lymphoid cell proliferation, and do not protec t cells from entering apoptosis. These in vitro findings may be useful for ALL clinical trial design.