Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia
- PMID: 14991544
- DOI: 10.1016/j.humpath.2003.08.020
Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia
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.
Similar articles
-
ATM mediates constitutive NF-kappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia.Oncogene. 2009 Feb 26;28(8):1099-109. doi: 10.1038/onc.2008.457. Epub 2008 Dec 15. Oncogene. 2009. PMID: 19079347
-
Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes.Clin Cancer Res. 1999 May;5(5):1115-24. Clin Cancer Res. 1999. PMID: 10353746
-
CD117/CD34 expression in leukemic blasts.Am J Clin Pathol. 1996 Aug;106(2):192-5. doi: 10.1093/ajcp/106.2.192. Am J Clin Pathol. 1996. PMID: 8712172
-
Chronic myelomonocytic leukaemia (CMML)--a myelodysplastic or myeloproliferative syndrome?Leuk Lymphoma. 1993 Jan;9(1-2):35-41. doi: 10.3109/10428199309148501. Leuk Lymphoma. 1993. PMID: 8477199 Review.
-
Relapse and cytogenetic evolution in myeloid neoplasms.Panminerva Med. 2017 Dec;59(4):308-319. doi: 10.23736/S0031-0808.17.03380-8. Panminerva Med. 2017. PMID: 29144072 Review.
Cited by
-
Frequency of inherited variants in the MEFV gene in myelodysplastic syndrome and acute myeloid leukemia.Int J Hematol. 2012 Mar;95(3):285-90. doi: 10.1007/s12185-012-1022-0. Epub 2012 Feb 18. Int J Hematol. 2012. PMID: 22351163
-
PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis.Mol Cancer Ther. 2020 Sep;19(9):1809-1821. doi: 10.1158/1535-7163.MCT-20-0160. Epub 2020 Aug 4. Mol Cancer Ther. 2020. PMID: 32753387 Free PMC article.
-
NF-kappaB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs).Blood. 2005 Dec 1;106(12):3917-25. doi: 10.1182/blood-2005-04-1424. Epub 2005 Aug 16. Blood. 2005. PMID: 16105982 Free PMC article.
-
Global H3K4me3 genome mapping reveals alterations of innate immunity signaling and overexpression of JMJD3 in human myelodysplastic syndrome CD34+ cells.Leukemia. 2013 Nov;27(11):2177-86. doi: 10.1038/leu.2013.91. Epub 2013 Mar 29. Leukemia. 2013. PMID: 23538751 Free PMC article.
-
The BCR-ABL/NF-κB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias.Oncotarget. 2016 Oct 4;7(40):66287-66298. doi: 10.18632/oncotarget.11507. Oncotarget. 2016. PMID: 27563822 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous