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

Eur J Haematol. 2007 Sep;79(3):210-25. doi: 10.1111/j.1600-0609.2007.00899.x. Epub 2007 Jul 26.

Abstract

Objectives: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Neoplasm / blood*
  • Antibody Formation
  • Antigens, Neoplasm
  • Case-Control Studies
  • Cell Differentiation
  • Cell Nucleus / chemistry
  • Cyclin B / analysis
  • Cyclin B / immunology*
  • Cyclin B1
  • Cytoplasm / chemistry*
  • Dendritic Cells
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / pathology*
  • Mice
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Transplantation, Heterologous

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CCNB1 protein, human
  • Ccnb1 protein, mouse
  • Cyclin B
  • Cyclin B1