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Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia.
- Source :
-
Human pathology [Hum Pathol] 2004 Feb; Vol. 35 (2), pp. 246-53. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Blotting, Western
Child
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, Myelomonocytic, Chronic pathology
Male
Middle Aged
Myelodysplastic Syndromes pathology
NF-kappa B metabolism
Prognosis
Proto-Oncogene Proteins c-bcl-2 analysis
Transcription Factor RelA
Transcriptional Activation
DNA-Binding Proteins analysis
Leukemia, Myeloid, Acute pathology
NF-kappa B analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0046-8177
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Human pathology
- Publication Type :
- Academic Journal
- Accession number :
- 14991544
- Full Text :
- https://doi.org/10.1016/j.humpath.2003.08.020