Surface molecules are important biomarkers for cell proliferation and differentiation and play important roles in cell function and cell interaction.Notch is a transmembrane receptor that regulates developmental processes and cell-fate decision.Histamine is used as an adjunct to immunotherapy in myelogenous leukemia, and regulates hematopoietic cell development.Thus, we investigated the effects of histamine on immunophenotype and Notch signaling in human HL-60 leukemia cells.Histamine(0.1-10lM)inhibited the colony-forming efficiency of HL-60 cells in a dose-dependent fashion and shifted the growth curve to the right.HL-60 cells were treated with histamine 0.1-1.0lM for 6days, and surface molecules were analyzed by flow cytometry. Histamine decreased CD49d positive cells by 74% while increasing CD31 positive cells by 53% as compared to controls.Histamine did not affect the expression of CD11b, CD14, CD34, CD44, CD54, CD49e, and CD62L.To examine Notch signaling in histamine-induced immunophenotype alterations in HL-60 cells, total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. The expressions of Notch1, Notch4, the ligands Jagged1, Delta4, and the downstream hairy enhancer of split 1 gene (HES1) were not significantly altered by histamine.In summary, this study demonstrated that histamine inhibited HL-60 cell growth and regulated immunophenotypes of CD49d and CD31. These effects are not mediated through the Notch signaling.