Abstract
Acute myeloid leukemia is a type of clonal hematopoietic stem cell disorder displaying different genetic abnormalities. The critical balance between the self-renewal and differentiation of leukemia stem cells are regulated by various genes and signaling pathways that are regulated by these genes. Wnt/ β-catenin signaling pathway controls the self-renewal of hematopoietic stem cells by the regulation of β-catenin. Akirin-2 is an evolutionarily conserved nuclear protein which is thought to play important roles in immunity, NFκB and Wnt/β-catenin signaling pathways. In this study, expression of Akirin-2 gene was investigated in the CD34+ hematopoietic stem cells of patients with high β-catenin gene expression. Our results showed that the expression level of Akirin-2 gene was significantly higher in CD34+ hematopoietic stem cells of patients compared to healthy subjects and Akirin-2 gene could have an important role in AML pathogenesis
References
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- Tan, X. 2008. Beta-catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development. Hepatology, 47:1667–1679.
- Wodarz, A., Nusse, R. 1998. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol, 14:59–88.
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Abstract
Akut miyeloid lösemi (AML), farklı genetik anomaliler gösteren bir grup klonal hematopoetik kök hücre bozukluğudur. Lösemik kök hücrelerin kendini yenileme ve farklılaşmaları arasındaki hassas dengeyi, çeşitli genler ve bu genlerin düzenlediği sinyal yolakları kontrol etmektedir. Wnt/β-katenin sinyal yolağı, β-kateninin regülasyonu aracılığıyla hematopoetik kök hücrelerin kendilerini yenilemelerini kontrol etmektedir. Akirin2 proteini ise, immünite, NFκB ve Wnt/β-katenin sinyal yolaklarında çok önemli rolleri olduğu düşünülen yüksek derecede korunmuşluk gösteren bir proteindir. Bu çalışmada β-katenin gen ekspresyonu yüksek olan AML hastalarının CD34+ hematopoetik kök hücrelerinde Akirin2 geninin ifadesi araştırılmıştır. Sonuç olarak Akirin2 gen ifadesinin AML hastalarının CD34+ hematopoetik kök hücrelerinde sağlıklı bireylere göre anlamlı derecede artmış olduğu tespit edilmiş ve Akirin2 geninin AML patogenezinde önemli rollerinin olabileceğine dair ilk veriler elde edilmiştir
References
- Beutler B, Moresco EM. 2008. Akirins versus infection. Nat Immunol, 9:7-9.
- Goto A, Matsushita K, Gesellchen V, El Chamy L, Kuttenkeuler D, Takeuchi O, Hoffman JA, Akira S, Boutros M, Reichhart JM. 2008. Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice. Nat Immunol, 9: 97-104.
- Holliday, R. 2006. Epigenetics: a historical overview.Epigenetics, 1: 76–80.
- Ilyas, M. 2005. Wnt signalling and the mechanistic basis of tumour development. J Pathol, 205: (2):130–144.
- Jemal, A., Siegel, R., Xu, J., Ward, E. 2010. Cancer statistics. CA Cancer J Clin, 2010;60:277–300.
- Murdoch, B., Chadwick, K., Martin, M, et al. 2003. Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo. Proc Natl Acad Sci USA, 100:3422–3427.
- Passegué, E., Jamieson, CH., Ailles, LE., Weissman, IL. 2003. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci U S A. 30;100 Suppl, 1:11842-9.
- Perez-Moreno, M., Jamora, C., Fuchs, E. 2003. Sticky business: orchestrating cellular signals at adherens junctions. Cell, 112, 535-548.
- Reya, T., Duncan , AW., Ailles, L., Domen, J., Scherer, DC., Willert, K., Hintz, L., Nusse, R., Weissman, IL. 2003. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature, 423:409-414.
- Scheller M, Schonheit J, Zimmermenn K, Leser U, Rosenbauer F, Leutz A. 2013. Cross talk between Wnt/β- catenin and Irf8 in leukemia progression and drug resistance. The Journal of Experimental Medicine, 210: 2239-2256.
- Stone, R.M., O’donnell, M.R., Sekeres, M.A. Acute Myeloid Leukemia. 2004. Hematology Am Soc Hematol Educ Program. 98-117.
- Tan, X. 2008. Beta-catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development. Hepatology, 47:1667–1679.
- Wodarz, A., Nusse, R. 1998. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol, 14:59–88.
- Woodward, W.A., Chen, M.S., Behbod, F., Rosen, J.M. On mammary stem cells. 2005. J Cell Sci, 118 (Pt 16):3585-94.
Details
| Other ID | JA84SC44HC |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | May 27, 2016 |
| Submission Date | May 1, 2016 |
| Published in Issue | Year 2016 |