TY - JOUR
T1 - Expression of Constitutively Active Nuclear-κB RelA Transcription Factor in Blasts of Acute Myeloid Leukemia
AU - Bueso-Ramos, Carlos E.
AU - Rocha, Frederico C.
AU - Shishodia, Shishir
AU - Medeiros, L. Jeffrey
AU - Kantarjian, Hagop M.
AU - Vadhan, Saroj
AU - Estrov, Zeev
AU - Smith, Terry L.
AU - Nguyen, Martin H.
AU - Aggarwal, Bharat B
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/2
Y1 - 2004/2
N2 - The nuclear transcription factor NF-κB regulates cell survival, proliferation, and differentiation. Little is known about NF-κB in myeloid malignancies. In this report, we assessed NF-κB in a group of myeloid neoplasms by using an electrophoretic mobility shift assay (FALSA) 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-κB 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-κB immunoreactivity in AML blasts but not in normal bone marrow. Bcl-2, a downstream molecule, was expressed in cases with elevated NF-κB, but not in cases with basal levels of NF-κB, suggesting that NF-κB is active and provides the cells with survival advantages in vivo. These results suggest that suppression of NF-κB may be a useful therapeutic strategy for a subset of patients with AML.
AB - The nuclear transcription factor NF-κB regulates cell survival, proliferation, and differentiation. Little is known about NF-κB in myeloid malignancies. In this report, we assessed NF-κB in a group of myeloid neoplasms by using an electrophoretic mobility shift assay (FALSA) 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-κB 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-κB immunoreactivity in AML blasts but not in normal bone marrow. Bcl-2, a downstream molecule, was expressed in cases with elevated NF-κB, but not in cases with basal levels of NF-κB, suggesting that NF-κB is active and provides the cells with survival advantages in vivo. These results suggest that suppression of NF-κB may be a useful therapeutic strategy for a subset of patients with AML.
KW - Bone marrow
KW - Leukemia
KW - Myelodysplastic syndrome
KW - NF-κB
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U2 - 10.1016/j.humpath.2003.08.020
DO - 10.1016/j.humpath.2003.08.020
M3 - Article
C2 - 14991544
AN - SCOPUS:10744224210
SN - 0046-8177
VL - 35
SP - 246
EP - 253
JO - Human Pathology
JF - Human Pathology
IS - 2
ER -