Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia.
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.
Bueso-Ramos
Carlos E
CE
Department of Hematopathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Rocha
Frederico C
FC
Shishodia
Shishir
S
Medeiros
L Jeffrey
LJ
Kantarjian
Hagop M
HM
Vadhan-Raj
Saroj
S
Estrov
Zeev
Z
Smith
Terry L
TL
Nguyen
Martin H
MH
Aggarwal
Bharat B
BB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002648:Child; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis* / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051996:Transcription Factor RelA; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA