Effects of human stem cell factor (c-kit ligand) on proliferation of myeloid leukemia cells: heterogeneity in response and synergy with other hematopoietic growth factors

摘要: A novel hematopoietic growth factor, the stem cell factor (SCF), for primitive progenitor cells has recently been purified and its gene cloned. In this study we tested mitogenic activity of recombinant human SCF on myeloid leukemia as well expression receptor. We have investigated proliferation 31 lines fresh leukemic blasts from 17 patients in a 72-hour 3H-thymidine uptake assay presence various concentrations (rh) alone or combination with saturating granulocyte- macrophage colony-stimulating (GM-CSF), G-CSF, M-CSF, interleukin-3 (IL-3), erythropoietin (EPO). Only five lines, but 12 acute (AML), significantly responded to SCF. The responding were promyelocytic, chronic myeloid, megakaryoblastic, erythroleukemia origin, blast preparations all French-American-British subtypes. Synergistic activities found GM-CSF, EPO, IL-3. To determine binding sites cells, used 125I- radiolabeled Scatchard analysis cross-linking studies. expressed 2,300 up 29,000 per cell. receptor was downregulated vitro by ligand. Cross-linking studies demonstrated 150-Kd surface leukemias. This suggests that may be an important either direct stimulus synergistic other cytokines. Furthermore, using polymerase chain reaction total RNA SCF-mRNA 30 suggesting autocrine mechanisms subgroup coexpression