Cbp
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.
PMID: 14991544 [PubMed - in process]