Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia

Hum Pathol. 2004 Feb;35(2):246-53. doi: 10.1016/j.humpath.2003.08.020.


The nuclear transcription factor NF-kappa B regulates cell survival, proliferation, and differentiation. Little is known about NF-kappa B in myeloid malignancies. In this report, we assessed NF-kappa B in a group of myeloid neoplasms by using an electrophoretic mobility shift assay (EMSA) and immunofluorescence methods in freshly isolated leukemia cells. We analyzed 30 cases of acute myeloid leukemia (AML), 5 cases of myelodysplastic syndrome (MDS), 3 cases of chronic myelomonocytic leukemia (CMML), 15 cases of chronic myeloid leukemia in chronic phase (CML-CP), and 2 cases of chronic myeloid leukemia in blast crisis (CML-BC). Unstimulated cells (bone marrow and peripheral blood) from 17 normal donors and apheresis samples from 6 peripheral blood stem cell donors treated with granulocyte colony-stimulating factor (G-CSF) were used as controls. When EMSA was used, NF-kappa B was elevated in 14 of 30 (47%) cases of AML, in both cases of CML-BC, and in all reference donors treated with G-CSF, but it was at basal levels in all cases of MDS and CML-CP and in normal donors (P = <.01). Immunofluorescence analysis confirmed strong nuclear RelA/NF-kappa B immunoreactivity in AML blasts but not in normal bone marrow. Bcl-2, a downstream molecule, was expressed in cases with elevated NF-kappa B, but not in cases with basal levels of NF-kappa B, suggesting that NF-kappa B is active and provides the cells with survival advantages in vivo. These results suggest that suppression of NF-kappa B may be a useful therapeutic strategy for a subset of patients with AML.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Child
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / metabolism
  • Electrophoretic Mobility Shift Assay
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myeloid, Acute / pathology*
  • Leukemia, Myelomonocytic, Chronic / pathology
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / pathology
  • NF-kappa B / analysis*
  • NF-kappa B / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Transcription Factor RelA
  • Transcriptional Activation


  • DNA-Binding Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factor RelA