Activation of Notch signal pathway is associated with a poorer prognosis in acute myeloid leukemia

详细信息    查看全文

• 作者：Xin Xu (1)
  Yu Zhao (1)
  Maozhong Xu (1)
  Qiuxin Dai (1)
  Wenjun Meng (1)
  Jiangang Yang (1)
  Rujuan Qin (1)
  
• 关键词：Acute myeloid leukemia ; Notch1 ; Jagged1 ; Delta1 ; Prognosis
• 刊名：Medical Oncology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：28
• 期：1-supp
• 页码：483-489
• 全文大小：231KB
• 参考文献：1. Gr?schel S, Lugthart S, Schlenk RF, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010; in press.
  2. Verhaak RG, Valk PJ. Genes predictive of outcome and novel molecular classification schemes in adult acute myeloid leukemia. Cancer Treat Res. 2009;145:67-3. CrossRef
  3. Stirewalt DL, Meshinchi S. Receptor tyrosine kinase alterations in AML—biology and therapy. Cancer Treat Res. 2009;145:85-08. CrossRef
  4. Park MH, Cho SA, Yoo KH, et al. Gene expression profile related to prognosis of acute myeloid leukemia. Oncol Rep. 2007;18:1395-02.
  5. El Kholy NM, Sallam MM, Ahmed MB, et al. Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells. Med Oncol. 2010; in press.
  6. Zhou FL, Zhang WG, Wei YC, et al. Involvement of oxidative stress in the relapse of acute myeloid leukemia. J Biol Chem. 2010; in press.
  7. Hughes DP. How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res. 2010;152:479-6. CrossRef
  8. Mehta K, Osipo C. Trastuzumab resistance: role for Notch signaling. ScientificWorldJournal. 2009;9:1438-8. CrossRef
  9. Hirose H, Ishii H, Mimori K, et al. Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. Oncol Rep. 2010;23:35-3.
  10. Fan X, Khaki L, Zhu TS, et al. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells. 2010;28:5-6.
  11. Ellisen LW, Bird J, West DC. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66:649-1. CrossRef
  12. Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 109-8.
  13. Muller PY, Janovjak H, Miseret A, Dobbie Z. Processing of gene expression data generated by quantitative real time RT-PCR. Biotechniques. 2002;6:2-.
  14. Roumier C, Fenaux P, Lafage M. New mechanisms of AML1 gene alteration in hematological malignancies. Leukemia. 2003;17:9-6. CrossRef
  15. Siar CH, Nakano K, Han PP, Nagatsuka H, Ng KH, Kawakami T. Differential expression of Notch receptors and their ligands in desmoplastic ameloblastoma. J Oral Pathol Med. 2010; in press.
  16. Zhang P, Yang Y, Zweidler-McKay PA, Hughes DP. Critical role of Notch signaling in osteosarcoma invasion and metastasis. Clin Cancer Res. 2008;14:2962-. CrossRef
  17. Wang M, Xue L, Cao Q, et al. Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma. Neoplasma. 2009;56:533-1. CrossRef
  18. Pui JC, Allman D, Xu L. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity. 1999;11:299-08. CrossRef
  19. Radtke F, Wilson A, Stark G. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity. 1999;10:547-8. CrossRef
  20. Gestblom C. The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas. Lab Invest. 1999;79:67-9.
  21. Grynfeld A, Pahlman S, Axelson H. Induced neuroblastoma cell differentiation, associated with transient HES-1 activity and reduced HASH-1 expression, is inhibited by notch1. Int J Cancer. 2000;88:401-0. CrossRef
  22. Li GH, Fan YZ, Liu XW, et al. Notch signaling maintains proliferation and survival of the HL60 human promyelocytic leukemia cell line and promotes the phosphorylation of the Rb protein. Mol Cell Biochem. 2010; in press.
  23. Itoh M, Fu L, Tohda S. NF-kappaB activation induced by Notch ligand stimulation in acute myeloid leukemia cells. Oncol Rep. 2009;22:631-.
  24. Yan S, Ma D, Ji M, et al. Expression profile of Notch-related genes in multidrug resistant K562/A02 cells compared with parental K562 cells. Int J Lab Hematol. 2009; in press.
  25. Chiaramonte R, Basile A, Tassi E, et al. A wide role for NOTCH1 signaling in acute leukemia. Cancer Lett. 2005;219:113-0. CrossRef
  26. Li L, Milner LA, Deng Y. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity. 1998;8:43-. CrossRef
  27. Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken B. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood. 2002;99:3398-03. CrossRef
  28. Tohda S, Nara N. Expression of Notch1 and Jagged1 proteins in acute myeloid leukemia cells. Leuk Lymphoma. 2001;42:467-2. CrossRef
  29. Shi TP, Xu H, Wei JF, et al. Association of low expression of Notch-1 and Jagged-1 in human papillary bladder cancer and shorter survival. J Urol. 2008;180:361-. CrossRef
  30. Jubb AM, Soilleux EJ, Turley H, et al. Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer. Am J Pathol. 2010;176:2019-8. CrossRef
  31. Santagata S, Demichelis F, Riva A, et al. JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res. 2004;64:6854-. CrossRef
  32. Eliasz S, Liang S, Chen Y, et al. Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway. Oncogene. 2010;in press.
  33. Shih AH, Holland EC. Notch signaling enhances nestin expression in gliomas. Neoplasia. 2006;8:1072-2. CrossRef
  
• 作者单位：Xin Xu (1)
  Yu Zhao (1)
  Maozhong Xu (1)
  Qiuxin Dai (1)
  Wenjun Meng (1)
  Jiangang Yang (1)
  Rujuan Qin (1)
  
  1. The Affiliated Jiangyin Hospital of Southeast University Medical College, 214400, Jiangyin, Jiangsu, Peoples Republic of China
  

文摘

Objective Notch signal pathway plays a fundamental role in regulating haematopoietic development. It is also an important mediator of growth and survival in several cancer types, with Notch pathway genes functioning as oncogenes or tumor suppressors in different cancers. However, the clinical role of Notch signal pathway in acute myeloid leukemia (AML) remains unclear. Methods To address this problem, we investigated the gene expression levels of Notch signal pathway members (Notch1, Jagged1 and Delta1) in bone marrow mononuclear cells by real-time quantitative PCR in a cohort of 100 patients with newly diagnosed de novo AML and normal marrow donors. The prognostic values of the three molecules in AML were also analyzed. Results Comparing with the normal controls, we show the transcriptional up-regulation of Notch1, Jagged1 and Delta1 in the bone marrow of AML patients with statistic differences (P?=?0.008, 0.01 and 0.01, respectively). In addition, univariate analysis of factors associated with relapse-free survival and overall survival showed a significantly shorter survival in the patients with unfavorable karyotype, higher Notch1 expression, higher Jagged1 expression, or higher Delta1 expression. Moreover, Cox proportional hazards multivariate analysis of the univariate predictors identified karyotype and gene expression levels of Notch1, Jagged1 and Delta1 as independent prognostic factors for relapse-free survival and overall survival. Furthermore, the prognostic significance of Notch1, Jagged1 and Delta1 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Conclusion Taken together, our data suggest for the first time that the activation of Notch pathway may indicate a poor prognosis in AML. Especially, Notch1, Jagged1 and Delta1 expression may be relevant prognostic markers in intermediate risk AML.