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Article

Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia

  • Authors:
    • Pei‑Pei Li
    • Kang Lu
    • Ling‑Yun Geng
    • Xiang‑Xiang Zhou
    • Xin‑Yu Li
    • Xin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
  • Pages: 4934-4938
    |
    Published online on: April 12, 2016
       https://doi.org/10.3892/mmr.2016.5111
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Abstract

The B-cell receptor (BCR) signaling pathway serves an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and has been identified as a novel and effective therapeutic target of CLL, with particular focus its kinase factor, BTK. Previous studies have focused on combining the BTK inhibitor with additional chemotherapeutic agents to improve the prognosis of patients with CLL. Further investigation into the mechanism of the BTK inhibitor would promote an understanding of the pathogenesis of CLL. The current study investigated the association between ibrutinib and the Wnt signaling pathway, additionally focussing upon one of its regulators, metadherin (MTDH), which has been identified to be overexpressed in CLL and is considered a promoter of the Wnt pathway. The experiments in the current study were performed in the MEC-1 CLL cell line. Results indicated that MTDH, β-catenin and lymphoid-enhancing factor-1 were inhibited subsequent to ibrutinib treatment. The results indicate that in CLL, ibrutinib is likely to possess an inhibitory role in Wnt signaling.
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1 

Keating MJ, O'Brien S, Albitar M, Lerner S, Plunkett W, Giles F, Andreeff M, Cortes J, Faderl S, Thomas D, et al: Early results of a chemoimmunotherapy regimen of fludarabine, cyclophos-phamide and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 23:4079–4088. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Badoux XC, Keating MJ, Wang X, O'Brien SM, Ferrajoli A, Faderl S, Burger J, Koller C, Lerner S, Kantarjian H and Wierda WG: Fludarabine, cyclophosphamide and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 117:3016–3024. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Li PP and Wang X: Role of signaling pathways and miRNAs in chronic lymphocytic leukemia. Chin Med J. 126:4175–4182. 2013.PubMed/NCBI

4 

Chen J and McMillan NA: Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic leukaemia. Cancer Biol Ther. 7:174–179. 2008. View Article : Google Scholar

5 

Ten Hacken E and Burger JA: Microenvironment dependency in chronic lymphocytic leukemia: The basis for new targeted therapies. Pharmacol Ther. 144:338–348. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Shain KH and Tao J: The B-cell receptor orchestrates environment-mediated lymphoma survival and drug resistance in B-cell malignancies. Oncogene. 33:4107–4113. 2014. View Article : Google Scholar

7 

Robak T and Robak P: BCR signaling in chronic lymphocytic leukemia and related inhibitors currently in clinical studies. Int Rev Immunol. 32:358–376. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, Herman SE, Tian X, Marti G, Soto S, et al: Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: A phase 2, single-arm trial. Lancet Oncol. 16:169–176. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Byrd JC, Czuczman MS, Fayad LE, et al National comprehension cancer network: Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015. J Natl Compr Canc Netw. 13:326–362. 2015.PubMed/NCBI

10 

Alinari L, Quinion C and Blum KA: Bruton's tyrosine kinase inhibitors in B-cell non-Hodgkin's lymphomas. Clin Pharmacol Ther. 97:469–477. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Da Roit F, Engelberts PJ, Taylor RP, Breij EC, Gritti G, Rambaldi A, Introna M, Parren PW, Beurskens FJ and Golay J: Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: Implications for combination therapy. Haematologica. 100:77–86. 2015. View Article : Google Scholar

12 

Herman SE, Mustafa RZ, Gyamfi JA, Pittaluga S, Chang S, Chang B, Farooqui M and Wiestner A: Ibrutinib inhibits BCR and NF-kB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood. 123:3286–3295. 2014. View Article : Google Scholar : PubMed/NCBI

13 

James RG, Biechele TL, Conrad WH, Camp ND, Fass DM, Major MB, Sommer K, Yi X, Roberts BS, Cleary MA, et al: Bruton's tyrosine kinase revealed as a negative regulator of Wnt- beta- catenin signaling. Sci Signal. 2:2009. View Article : Google Scholar

14 

Yang Y, Shi J, Gu Z, Salama ME, Das S, Wendlandt E, Xu H, Huang J, Tao Y, Hao M, et al: Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res. 75:594–604. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Gutierrez A Jr, Tschumper RC, Wu X, Shanafelt TD, Eckel-Passow J, Huddleston PM III, Slager SL, Kay NE and Jelinek DF: LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood. 116:2975–2983. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Ge X, Lv X, Feng L, Liu X, Gao J, Chen N and Wang X: Metadherin contributes to the pathogenesis of diffuse large B-cell lymphoma. PLoS One. 7:e394492012. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

18 

Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ, et al: Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 117:6287–6296. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Li P, Feng LL, Chen N, Ge XL, Lv X, Lu K, Ding M, Yuan D and Wang X: Metadherin contributes to the pathogenesis of chronic lymphocytic leukemia partially through Wnt/β-catenin pathway. Med Oncol. 32:4792015. View Article : Google Scholar

20 

Maddocks K, Christian B, Jaglowski S, Flynn J, Jones JA, Porcu P, Wei L, Jenkins C, Lozanski G, Byrd JC and Blum KA: A phase 1/1b study of rituximab, bendamustine and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma. Blood. 125:242–248. 2015. View Article : Google Scholar

21 

Hallek M, Kay NE, Osterborg A, Chanan-Khan AA, Mahler M, Salman M, Wan Y, Sun S, Zhuang SH and Howes A: The helios trial protocol: A Phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia. Future Oncol. 11:51–59. 2015. View Article : Google Scholar

22 

Cheng S, Guo A, Lu P, Ma J, Coleman M and Wang YL: Functional characterization of BTK (C481S) mutation that confers ibrutinib resistance: Exploration of alternative kinase inhibitors. Leukemia. 29:885–900. 2015. View Article : Google Scholar

23 

Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, Byrd JC, Czuczman MS, Fayad LE, et al National comprehensive cancer network: Non-Hodgkin's lymphomas, version 4.2014. J Natl Compr Canc Netw. 12:1282–1303. 2014.PubMed/NCBI

24 

Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS, Xue L, Li DH, Steggerda SM, Versele M, et al: Resistance mechanisms for the bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med. 370:2286–2294. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY, de Weerdt I, Jeyakumar G, Ferrajoli A, Cardenas-Turanzas M, et al: Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: A single-arm, phase 2 study. Lancet Oncol. 15:1090–1099. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Logan CY and Nusse R: The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 20:781–810. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Nusse R: Wnt signaling in disease and in development. Cell Res. 15:28–32. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Gough NR: Focus issue: Wnt and β- catenin signaling in development and disease. Sci Signal. 5:2012. View Article : Google Scholar

29 

Gordon MD and Nusse R: Wnt signaling: Multiple pathways, multiple receptors and multiple transcription factors. J Biol Chem. 281:22429–22433. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Memarian A, Hojjat-Farsangi M, Asgarian-Omran H, Younesi V, Jeddi-Tehrani M, Sharifian RA, Khoshnoodi J, Razavi SM, Rabbani H and Shokri F: Variation in Wnt genes expression in different subtypes of chronic lymphocytic leukemia. Leuk Lymphoma. 50:2061–2070. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Lu D, Zhao Y, Tawatao R, Cottam HB, Sen M, Leoni LM, Kipps TJ, Corr M and Carson DA: Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 101:3118–3123. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, Schmitt EK, Hallek M and Kreuzer KA: Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Neoplasia. 12:326–335. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Gandhirajan RK, Poll-Wolbeck SJ, Gehrke I and Kreuzer KA: Wnt/β-catenin/LEF-1 signaling in chronic lymphocytic leukemia (CLL): A target for current and potential therapeutic options. Curr Cancer Drug Targets. 10:716–727. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Lu D, Liu JX, Endo T, Zhou H, Yao S, Willert K, Schmidt-Wolf IG, Kipps TJ and Carson DA: Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway. PLoS One. 4:e82942009. View Article : Google Scholar : PubMed/NCBI

35 

Lu D, Choi MY, Yu J, Castro JE, Kipps TJ and Carson DA: Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci USA. 108:13253–13257. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Li P, Yao QM, Zhou H, Feng LL, Ge XL, Lv X, Chen N, Lu K and Wang X: Metadherin contribute to BCR signaling in chronic lymphocytic leukemia. Int J Clin Exp Pathol. 7:1588–1594. 2014.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li PP, Lu K, Geng LY, Zhou XX, Li XY and Wang X: Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia. Mol Med Rep 13: 4934-4938, 2016.
APA
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., & Wang, X. (2016). Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia. Molecular Medicine Reports, 13, 4934-4938. https://doi.org/10.3892/mmr.2016.5111
MLA
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., Wang, X."Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia". Molecular Medicine Reports 13.6 (2016): 4934-4938.
Chicago
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., Wang, X."Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia". Molecular Medicine Reports 13, no. 6 (2016): 4934-4938. https://doi.org/10.3892/mmr.2016.5111
Copy and paste a formatted citation
x
Spandidos Publications style
Li PP, Lu K, Geng LY, Zhou XX, Li XY and Wang X: Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia. Mol Med Rep 13: 4934-4938, 2016.
APA
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., & Wang, X. (2016). Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia. Molecular Medicine Reports, 13, 4934-4938. https://doi.org/10.3892/mmr.2016.5111
MLA
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., Wang, X."Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia". Molecular Medicine Reports 13.6 (2016): 4934-4938.
Chicago
Li, P., Lu, K., Geng, L., Zhou, X., Li, X., Wang, X."Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia". Molecular Medicine Reports 13, no. 6 (2016): 4934-4938. https://doi.org/10.3892/mmr.2016.5111
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