Correlation between p65 and TNF-α in patients with acute myelocytic leukemia

Dong,Qiao‑Mei; Ling,Chun; Zhu,Jun‑Fang; Chen,Xuan; Tang,Yan; Zhao,Li

doi:10.3892/ol.2015.3720

Correlation between p65 and TNF-α in patients with acute myelocytic leukemia

Authors:
- Qiao‑Mei Dong
- Chun Ling
- Jun‑Fang Zhu
- Xuan Chen
- Yan Tang
- Li Zhao
View Affiliations

Affiliations: Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Published online on: September 17, 2015 https://doi.org/10.3892/ol.2015.3720
Pages: 3305-3309

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The correlation between the expression levels of p65 and TNF-α in patients with acute myelocytic leukemia (AML) and AML cell lines were investigated. The bone marrow samples of 30 AML patients and 10 non‑leukemia controls were studied. The mRNA expression levels of p65 and TNF‑α were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and Pearson's Correlation test was used to demonstrate the correlation between TNFα and p65 expression levels in AML specimens. Receiver operating characteristic (ROC) curves were plotted to determine whether TNFα and p65 expression levels could be used to differentiate AML samples from non‑leukemia samples. MG132 and anti‑TNFα antibody were used to inhibit the expression of p65 and TNF‑α in the AML cell line, HL‑60. The expression of p65 and TNF‑α were detected by RT‑qPCR and western blot analysis. The mRNA expression levels of p65 and TNF‑α were significantly increased in AML patients compared with non‑leukemia control bone marrow samples by RT‑qPCR, and the two molecules expression pattern's exhibited sufficient predictive power to distinguish AML patients from non‑leukemia control samples. Pearson's correlation analysis demonstrated that TNFα expression was strongly correlated with p65 expression in AML bone marrow samples. In HL‑60 cells, inhibition of TNFα reduced the expression of p65; in addition, inhibition of p65 reduced the expression of TNFα as assessed by RT‑qPCR and western blot analysis. p65 and TNF‑α were highly expressed in AML patients, and these 2 molecules were strongly correlated. The present study indicates that p65 and TNF‑α have potential as molecular markers to distinguish AML patients from non-leukemia control samples, and that these 2 molecules may be useful prognostic factor for patients with AML.

View Figures

View References

1	Larkin K and Blum W: Novel therapies in AML: Reason for hope or just hype? Am Soc Clin Oncol Educ Book. e341–e351. 2014. View Article : Google Scholar : PubMed/NCBI
2	Kohgo Y, Inamura J and Shindo M: Molecular target drugs for AML-current state and prospects for the future. Nihon Rinsho. 72:1063–1067. 2014.(In Japanese). PubMed/NCBI
3	Zeijlemaker W, Gratama JW and Schuurhuis GJ: Tumor heterogeneity makes AML a ‘moving target’ for detection of residual disease. Cytometry B Clin Cytom. 86:3–14. 2014. View Article : Google Scholar : PubMed/NCBI
4	Thomas R, Phuong J, McHale CM and Zhang L: Using bioinformatic approaches to identify pathways targeted by human leukemogens. Int J Environ Res Public Health. 9:2479–2503. 2012. View Article : Google Scholar : PubMed/NCBI
5	Liu YQ, Zhao FJ and Chen WQ: An analysis of incidence and mortality of leukemia in China, 2009. Zhong Guo Ai Zheng Yan Jiu. 22:528–534. 2013.(In Chinese).
6	Miyawaki S: Guideline for AML. Rinsho Ketsueki. 54:1633–1642. 2013.(In Japanese). PubMed/NCBI
7	Levine RL: Molecular pathogenesis of AML: Translating insights to the clinic. Best Pract Res Clin Haematol. 26:245–248. 2013. View Article : Google Scholar : PubMed/NCBI
8	Al-Ali HK, Jaekel N and Niederwieser D: The role of hypomethylating agents in the treatment of elderly patients with AML. J Geriatr Oncol. 5:89–105. 2014. View Article : Google Scholar : PubMed/NCBI
9	Kamieńska E, Ociepa T, Wysocki M, Kurylak A, Matysiak M, Urasiński T, Urasińska E and Domagała W: Activation of NF-kB in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukaemia: Relation to other prognostic factors. Pol J Pathol. 62:5–11. 2011.PubMed/NCBI
10	Giuliani C, Napolitano G, Bucci I, Montani V and Monaco F: Nf-kB transcription factor: Role in the pathogenesis of inflammatory, autoimmune and neoplastic diseases and therapy implications. Clin Ter. 152:249–253. 2001.(In Italian). PubMed/NCBI
11	Baud V and Jacque E: The alternative NF-kB activation pathway and cancer: friend or foe? Med Sci (Paris). 24:1083–1088. 2008.(In French). View Article : Google Scholar : PubMed/NCBI
12	Schulz U, Munker R, Ertl B, Holler E and Kolb HJ: Different types of human leukemias express the message for TNF-alpha and interleukin-10. Eur J Med Res. 6:359–363. 2001.PubMed/NCBI
13	Sun Y, Mi W, Cai J, Ying W, Liu F, Lu H, Qiao Y, Jia W, Bi X, Lu N, et al: Quantitative proteomic signature of liver cancer cells: Tissue transglutaminase 2 could be a novel protein candidate of human hepatocellular carcinoma. J Proteome Res. 7:3847–3859. 2008. View Article : Google Scholar : PubMed/NCBI
14	Zor T and Zvi S: Linearization of the Bradford protein assay increases its sensitivity: Theoretical and experimental studies. Anal Biochem. 236:302–308. 1996. View Article : Google Scholar : PubMed/NCBI
15	Karatas OF, Guzel E, Suer I, Ekici ID, Caskurlu T, Creighton CJ, Ittmann M and Ozen M: miR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer. PLoS One. 9:e986752014. View Article : Google Scholar : PubMed/NCBI
16	Morotti A, Cilloni D, Pautasso M, Messa F, Arruga F, Defilippi I, Carturan S, Catalano R, Rosso V, Chiarenza A, et al: NF-kB inhibition as a strategy to enhance etoposide-induced apoptosis in K562 cell line. Am J Hematol. 81:938–945. 2006. View Article : Google Scholar : PubMed/NCBI
17	Abdullah M, Rani AA, Sudoyo AW, Makmun D, Handjari DR and Hernowo BS: Expression of NF-kB and COX2 in colorectal cancer among native Indonesians: The role of inflammation in colorectal carcinogenesis. Acta Med Indones. 45:187–192. 2013.PubMed/NCBI
18	Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM and Jordan CT: Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 98:2301–2307. 2001. View Article : Google Scholar : PubMed/NCBI
19	Choi S, Park YS, Koga T, Treloar A and Kim KC: TNF-α is a key regulator of MUC1, an anti-inflammatory molecule, during airway Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol. 44:255–260. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zhu M, Zhu Y and Lance P: TNF α-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells. Cell Prolif. 46:374–381. 2013. View Article : Google Scholar : PubMed/NCBI
21	Rivas MA, Carnevale RP, Proietti CJ, Rosemblit C, Beguelin W, Salatino M, Charreau EH, Frahm I, Sapia S, Brouckaert P, et al: TNF alpha acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-kappa B-dependent pathways. Exp Cell Res. 314:509–529. 2008. View Article : Google Scholar : PubMed/NCBI
22	Lee YR, Yu HN, Noh EM, Youn HJ, Song EK, Han MK, Park CS, Kim BS, Park YS, Park BK, et al: TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells. Exp Mol Med. 39:121–127. 2007. View Article : Google Scholar : PubMed/NCBI
23	Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y and Kurokawa M: Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity. J Clin Invest. 124:528–542. 2014. View Article : Google Scholar : PubMed/NCBI