Steel factor (SLF,
c-kit ligand), a potent costimulating
cytokine in vitro for myeloid progenitor cells from normal donors, is currently being evaluated in clinical trials for effects on hematopoiesis. Based on a preliminary observation that
colony-stimulating factor (CSF)-responsive myeloid progenitor cells (CFU-GM) from a few patients with
acute myeloid leukemia (AML) did not respond to the costimulating effects of SLF, we evaluated responsiveness of bone marrow or blood CFU-GM from 26 patients with either AML,
chronic myeloid leukemia (CML) or
myelodysplastic syndrome (MDS) to the effects in vitro of SLF and/or granulocyte-macrophage
CSF (GM-CSF). Cells from all 26 patients responded to the stimulating effects of
GM-CSF, but marked heterogeneity was detected in each disease category to the costimulating effects of SLF. Nine of 13 patients with AML, 2 of 6 patients with CML and 4 of 7 patients with MDS had clonogenic cells that did not respond significantly to the costimulating effects of SLF. In a more limited study of cells from patients with MDS, it was noted that if the CFU-GM of that patient did not respond to SLF enhancement of CSF-induced colony formation, neither did the
erythropoietin (Epo)-dependent erythroid (BFU-E) or multipotential (CFU-GEMM) cells of that patient (3 cases of
refractory anemia [RA] evaluating bone marrow and in 1 case blood progenitors as well). If CFU-GM responded, BFU-E and CFU-GEMM responded (bone marrow from 1 patient with
chronic myelomonocytic leukemia [CMMol]). Clinical criteria did not readily distinguish between patients who had SLF-responsive vs. -nonresponsive clonogenic cells. While the mechanistic reason for this heterogeneity in responsiveness is not clear, these differences should be carefully considered for possible clinical trials with SLF in patients with acute and
chronic myeloid leukemia and MDS.