EFFECT OF STEM-CELL FACTOR ON LEUKEMIC PROGENITOR-CELL GROWTH AND SENSITIVITY TO CYTOSINE-ARABINOSIDE

Recruitment of quiescent, clonogenic blasts from patients with acute m yeloid leukemia (AML) by hematopoietic growth factors (HGFs) may impro ve the cytotoxic effects of cell-cycle-specific drugs like cytosine-ar abinoside (Ara-C). Using the culture methods described by Nara and McC ulloch and making a distinction between self-renewing and post-determi nistic mitoses, we analyzed the effects of stem cell factor (SCF), a g rowth factor acting on early hematopoietic progenitor and stem cells. First, we demonstrated that SCF, used in combination with other HGFs i ncluded in fetal calf serum (FCS) and/or in 5637 cell line supernatant (5637-CM), stimulated both colony formation and self-renewal of blast progenitors from 10 patients, unlike SCF alone. We tested the effects of SCF on the recruitment of cells in the S-phase by using a bromodeo xyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM). We showed that SCF stimulated proliferation of AML cells significantly i n 9/18 patients with AML. Second, we tested the influence of SCF on th e sensitivity to Ara-C of self-renewing leukemic cells from 18 patient s with AML. We showed that SCF was efficient in increasing the toxicit y of Ara-C on the self-renewing blast progenitors, especially with hig h concentrations of Ara-C. However, a large patient-to-patient heterog eneity was found and the activity of SCF was not correlated with its e ffect on the cell cycle, These data indicate that SCF can enhance sens itivity to Ara-C of some leukemic cells with self-renewing capacity. C opyright (C) 1996 Elsevier Science Ltd