Cyclin B1 is commonly expressed in the cytoplasm of primary human acute myelogenous leukemia cells and serves as a leukemia-associated antigen associated with autoantibody response in a subset of patients

Objective: Aberrant expression of cyclin B1, a cell cycle regulator, is related to prognosis in various human malignancies. Additionally, cytoplasmic expression of cyclin B1 in epithelial malignancies is associated with a specific T-cell response and presumably also a humoral immune response. We therefore investigated (i) whether a similar expression pattern could be detected in native human acute myelogenous leukemia (AML) cells and (ii) whether cyclin B1 specific antibodies could be detected in AML. Methods: AML cell expression of cyclin B1 was analyzed by flow cytometry and confocal microscopy. Humoral immune response in AML patient sera against cyclin B1 was analyzed by ELISA. Results: AML cell expression of cyclin B1 was detected for all 42 patients; but the percentage of cyclin B1 positive cells showed a wide variation between patients. Confocal microscopy demonstrated that 32/42 (76%) patient samples showed abnormal cytoplasmic expression. Furthermore, the cytoplasmic expression was maintained after 14 d of in vitro culture and differentiation of the AML cells towards a dendritic cell phenotype. Cyclin B1 specific serum antibodies could be detected for seven of 65 patients with untreated AML. Colclusions: Our studies demonstrate that primary human AML cells show aberrant cytoplasmic expression of cyclin B1 for a majority of patients and a specific humoral immune response was also detected for a subset of patients with untreated leukemia.