[Home ] [Archive]   [ فارسی ]  
:: Main :: About us :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 15, Issue 2 (Summer 2018) ::
Sci J Iran Blood Transfus Organ 2018, 15(2): 149-164 Back to browse issues page
The role of Wnt/β-catenin signaling pathway in blood leukemias
M. Ghari Dr., E. Fathi Dr. * , R. Farahzadi Dr.
Associate Professor University of Tabriz
Keywords: Key words: Wnt Signaling Pathway, Leukemia, Chronic Myeloid, Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Chronic Lymphocytic Leukemia
Full-Text [PDF 799 kb]   (68 Downloads)     |   Abstract (HTML)  (164 Views)
Type of Study: Review Article | Subject: Hematology
Full-Text:   (25 Views)
References:
  1. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell 2008; 132(4): 631-44.
  2. Lento W, Congdon K, Voermans C, Kritzik M, Reya T. Wnt signaling in normal and malignant hematopoiesis. Cold Spring Harb Perspect Biol 2013; 5(2): pii: a008011.
  3. Staal FJ, Chhatta A, Mikkers H. Caught in a Wnt storm: Complexities of Wnt signaling in hematopoiesis. Exp Hematol 2016; 44(6): 451-7.
  4. Luis TC, Ichii M, Brugman MH, Kincade P, Staal FJ. Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in
 
leukemia development. Leukemia 2012; 26(3): 414-21.
  1. Malhotra S, Kincade PW. Wnt-related molecules and signaling pathway equilibrium in hematopoiesis. Cell Stem Cell 2009; 4(1): 27-36.
  2. Khan Z, Arafah M, Shaik J, Mahale A, Alanazi M. High-frequency deregulated expression of Wnt signaling pathway members in breast carcinomas. OncoTargets Ther 2018; 11(35): 323-35.
  3. Tan Z, Zheng H, Liu X, Zhang W, Zhu J, Wu G, et al. MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/beta  -   catenin   signaling    in   breast   cancer.
Oncotarget 2016; 7(17): 24076-87.
  1. Zhou D, Tang W, Wang W, Pan X, An HX, Zhang Y. Association between aberrant APC promoter methylation and breast cancer pathogenesis: a meta-analysis of 35 observational studies. Peer J 2016; 4: e2203.
  2. Slattery M, Mullany L, Sakoda L, S. Samowitz W, K. Wolff R, Stevens J, et al. Expression of wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer. Modern Pathol 2017; 30(8): 1152-69.
  3. Liu H, Zhou Y, Tan F, Wang Y, Pei H. Expression of regulatory factor R-spondin family in Wnt signaling pathway in colorectal cancer and its clinical significance. Journal of Central South University. Med Sci 2017; 42(5): 501-6.
  4. Dhaya B. Targeting the interaction of Aurora kinases and SIRT1 mediated by Wnt signaling pathway in colorectal cancer: A critical review. Biomed Pharmacother 2016; 82: 413-24.
  5. Staal FJ, Luis TC, Tiemessen MM. WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 2008; 8(8): 581-93.
  6. Staal FJ, Sen JM. The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol 2008; 38(7): 1788-94.
  7. MacDonald BT, Tamai K, He X. Wnt/beta-catenin
signaling: components, mechanisms, and diseases. Dev Cell 2009; 17(1): 9-26.
  1. Wilusz M, Majka M. Role of the Wnt/beta-catenin network in regulating hematopoiesis. Arch Immunol Ther Exp (Warsz) 2008; 56(4): 257-66.
  2. Filipovich A, Gehrke I, Poll-Wolbeck SJ, Kreuzer KA. Physiological inhibitors of Wnt signaling. Eur J Haematol 2011; 86(6): 453-65.
  3. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 2004; 303(5663): 1483-7.
  4. Gholizadeh-Ghaleh Aziz S, Fathi E, Rahmati-Yamchi M, Akbarzadeh A, Fardyazar Z, Pashaiasl M. An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering. Artif Cells Nanomed Biotechnol 2017; 45(4): 765-74.
  5. Fathi E, Farahzadi R, Charoudeh HN. L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/beta-catenin and PKA pathway. Exp Biol Med (Maywood) 2017; 242(5): 482-6.
  6. Fathi E, Farahzadi R. Enhancement of osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells by zinc sulphate under electromagnetic field via the PKA, ERK1/2 and Wnt/beta-catenin signaling pathways. PLoS One 2017; 12(3): e0173877.
  7. Sampson  EM,  Haque  ZK,  Ku  MC,   Tevosian   SG,
Albanese C, Pestell RG, et al. Negative regulation of the Wnt-beta-catenin pathway by the transcriptional repressor HBP1. EMBO J 2001; 20(16): 4500-11.
  1. Hankey W, L. Frankel W, Groden J. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting. Cancer Metastasis Rev 2018; 37(1): 159-72.
  2. Morgan R, Ankrah R, El-Tanani S, Loadman P, Pattterson L, Rudland P, et al. Wnt Signaling as a Therapeutic Target in Cancer and Metastasis. Introduction to Cancer Metastasis. Chapter 20; 2017. p. 375-94.
  3. Sakanaka C, Sun TQ, Williams LT. New steps in the Wnt/beta-catenin signal transduction pathway. Recent Prog Horm Res 2000; 55: 225-36.
  4. Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci 1999; 56(5-6): 523-37.
  5. Porfiri E, Rubinfeld B, Albert I, Hovanes K, Waterman M, Polakis P. Induction of a beta-catenin-LEF-1 complex by wnt-1 and transforming mutants of beta-catenin. Oncogene 1997; 15(23): 2833-9.
  6. Staal FJ, Famili F, Garcia Perez L, Pike-Overzet K. Aberrant Wnt Signaling in Leukemia. Cancers (Basel) 2016; 8(9): 78-92.
  7. Zhan T, Rindtorrf N, Boutros M. Wnt signaling in cancer. Oncogene 2017; 36: 1461-73.
  8. Luis TC, Naber BA, Roozen PP, Brugman MH, de Haas EF, Ghazvini M, et al. Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion. Cell Stem Cell 2011; 9(4): 345-56.
  9. Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999; 341(14): 1051-62.
  10. Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, et al. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol 2004; 24(7): 2890-904.
  11. Corces-Zimmerman MR, Majeti R. Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis. Leukemia 2014; 28(12): 2276-82.
  12. Zheng X, Beissert T, Kukoc-Zivojnov N, Puccetti E, Altschmied J, Strolz C, et al. Gamma-catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells. Blood 2004; 103(9): 3535-43.
  13. Ysebaert L, Chicanne G, Demur C, De Toni F, Prade-Houdellier N, Ruidavets JB, et al. Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia 2006; 20(7): 1211-6.
  14. Morgan RG, Pearn L, Liddiard K, Pumford SL, Burnett AK, Tonks A, et al. gamma-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of beta-catenin. Leukemia 2013; 27(2): 336-43.
  15. Griffiths EA, Gore SD, Hooker C, McDevitt MA, Karp JE, Smith BD, et al. Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation.   Leuk    Lymphoma 2010; 51(9):
1711-9.
  1. Ying J, Li H, Chen YW, Srivastava G, Gao Z, Tao Q. WNT5A is epigenetically silenced in hematologic malignancies and inhibits leukemia cell growth as a tumor suppressor. Blood 2007; 110(12): 4130-2.
  2. Liang  H,  Chen  Q, Coles AH, Anderson SJ, Pihan G,
Bradley A, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell 2003; 4(5): 349-60.
  1. Martin V, Valencia A, Agirre X, Cervera J, San Jose-Eneriz E, Vilas-Zornoza A, et al. Epigenetic regulation of the non-canonical Wnt pathway in acute myeloid leukemia. Cancer Sci 2010; 101(2): 425-32.
  2. Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, et al. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010; 327(5973): 1650-3.
  3. Tickenbrock L, Schwable J, Wiedehage M, Steffen B, Sargin B, Choudhary C, et al. Flt3 tandem duplication mutations cooperate with Wnt signaling in leukemic signal transduction. Blood 2005; 105(9): 3699-706.
  4. Xu J, Suzuki M, Niwa Y, Hiraga J, Nagasaka T, Ito M, et al. Clinical significance of nuclear non-phosphorylated beta-catenin in acute myeloid leukaemia and myelodysplastic syndrome. Br J Haematol 2008; 140(4): 394-401.
  5. Taskesen E, Staal FJ, Reinders MJ. An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in acute myeloid leukemia. BMC Bioinformatics 2015; 16 Suppl 4: S4.
  6. Guezguez B, Almakadi M, Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn A, et al. GSK3 Deficiencies in Hematopoietic Stem Cells Initiate Pre-neoplastic State that Is Predictive of Clinical Outcomes of Human Acute Leukemia. Cancer Cell 2016; 29(1): 61-74.
  7. Majeti R, Becker MW, Tian Q, Lee TL, Yan X, Liu R, et al. Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. Proc Natl Acad Sci U S A 2009; 106(9): 3396-401.
  8. Beghini A, Corlazzoli F, Del Giacco L, Re M, Lazzaroni F, Brioschi M, et al. Regeneration-associated WNT signaling is activated in long-term reconstituting AC133bright acute myeloid leukemia cells. Neoplasia 2012; 14(12): 1236-48.
  9. Minke KS, Staib P, Puetter A, Gehrke I, Gandhirajan RK, Schlosser A, et al. Small molecule inhibitors of WNT signaling effectively induce apoptosis in acute myeloid leukemia cells. Eur J Haematol 2009; 82(3): 165-75.
  10. Fiskus W, Sharma S, Saha S, Shah B, Devaraj SG, Sun B, et al. Pre-clinical efficacy of combined therapy with novel beta-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells. Leukemia 2015; 29(6): 1267-78.
  11. Heidel FH, Arreba-Tutusaus P, Armstrong SA, Fischer T. Evolutionarily conserved signaling pathways: acting in the shadows of acute myelogenous leukemia's genetic diversity. Clin Cancer Res 2015; 21(2): 240-8.
  12. Thanendrarajan   S,   Kim   Y,     Schmidt-    Wolf IG.
Understanding and Targeting the Wnt/beta-Catenin Signaling Pathway in Chronic Leukemia. Leuk Res Treatment 2011; 2011: 329572.
  1. Weerkamp F, Dekking E, Ng YY, van der Velden VH, Wai H, Bottcher S, et al. Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in leukemia patients. Leukemia 2009; 23(6): 1106-17.
  2. Nowicki MO, Pawlowski P, Fischer T, Hess G, Pawlowski T, Skorski T. Chronic myelogenous leukemia molecular signature. Oncogene 2003; 22(25): 3952-63.
  3. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL,  et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004; 351(7): 657-67.
  4. Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM, et al. Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 2007; 12(6): 528-41.
  5. Yu S, Li F, Xing S, Zhao T, Peng W, Xue HH. Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1 Transcription Factors. J Biol Chem 2016; 291(21): 11148-60.
  6. Gregory MA, Phang TL, Neviani P, Alvarez-Calderon F, Eide CA, O'Hare T, et al. Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl. Cancer Cell 2010; 18(1): 74-87.
  7. Hu Y, Li S. Survival regulation of leukemia stem cells. Cell Mol Life Sci 2016; 73(5): 1039-50.
  8. Heidel FH, Bullinger L, Feng Z, Wang Z, Neff TA, Stein L, et al. Genetic and pharmacologic inhibition of beta-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell 2012; 10(4): 412-24.
  9. Reya T, O'Riordan M, Okamura R, Devaney E, Willert K, Nusse R, et al. Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity 2000; 13(1): 15-24.
  10. Ranheim EA, Kwan HC, Reya T, Wang YK, Weissman IL, Francke U. Frizzled 9 knock-out mice have abnormal B-cell development. Blood 2005; 105(6): 2487-94.
  11. McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR, Murre C. Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia. Proc Natl Acad Sci U S A 1999; 96(20): 11464-9.
  12. Nygren MK, Dosen G, Hystad ME, Stubberud H, Funderud S, Rian E. Wnt3A activates canonical Wnt signalling in acute lymphoblastic leukaemia (ALL) cells and inhibits the proliferation of B-ALL cell lines. Br J Haematol 2007; 136(3): 400-13.
  13. Nygren MK, Dosen-Dahl G, Stubberud H, Walchli S, Munthe E, Rian E. beta-catenin is involved in N-cadherin-dependent adhesion, but not in canonical Wnt signaling in E2A-PBX1-positive B acute lymphoblastic leukemia cells. Exp Hematol 2009; 37(2): 225-33.
  14. Saba NS, Angelova M, Lobelle-Rich PA, Levy LS. Disruption of pre-B-cell receptor signaling jams the WNT/beta-catenin pathway and induces cell death in B-cell acute lymphoblastic leukemia cell lines. Leuk Res 2015; pii: S0145-2126(15)30355-6.
  15. Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlosser A, et al. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Neoplasia 2010; 12(4): 326-35.
  16. Lu D, Zhao Y, Tawatao R, Cottam HB, Sen M, Leoni LM, et al. Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2004; 101(9): 3118-23.
  17. Chim CS, Fung TK, Wong KF, Lau JS, Liang R. Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia. Leuk Res 2006; 30(9): 1135-9.
  18. Chim CS, Pang R, Fung TK, Choi CL, Liang R. Epigenetic dysregulation of Wnt signaling pathway in multiple myeloma. Leukemia 2007; 21(12): 2527-36.
  19. Liu R, Wang L, Chen C, Liu Y, Zhou P, Wang Y, et al. Laforin negatively regulates cell cycle progression through glycogen synthase kinase 3beta-dependent mechanisms. Mol Cell Biol 2008; 28(23): 7236-44.
  20. Gutierrez NC, Ocio EM, de Las Rivas J, Maiso P, Delgado M, Ferminan E, et al. Gene expression profiling of B lymphocytes and plasma cells from Waldenstrom's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals. Leukemia 2007; 21(3): 541-9.
  21. Janovska P, Poppova L, Plevova K, Plesingerova H, Behal M, Kaucka M, et al. Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia. Clin Cancer Res 2016; 22(2): 459-69.
  22. Izon DJ, Punt JA, Pear WS. Deciphering the role of Notch signaling in lymphopoiesis. Curr Opin Immunol 2002; 14(2): 192-9.
  23. Jenkinson EJ, Jenkinson WE, Rossi SW, Anderson G. The thymus and T-cell commitment: the right niche for Notch? Nat Rev Immunol 2006; 6(7): 551-5.
  24. Lee SY, Kumano K, Masuda S, Hangaishi A, Takita J, Nakazaki K, et al. Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia: analysis in adults and children. Leukemia 2005; 19(10): 1841-3.
  25. Weerkamp F, van Dongen JJ, Staal FJ. Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia. Leukemia 2006; 20(7): 1197-205.
  26. Weng AP, Ferrando AA, Lee W, Morris JPt, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306(5694): 269-71.
  27. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006; 20(15): 2096-109.
  28. Yokota T, Kanakura Y. Genetic abnormalities associated with acute lymphoblastic leukemia. Cancer
Sci 2016; 107(6): 721-5.
  1. Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, et al. A critical role for TCF-1 in T-lineage specification and differentiation. Nature 2011; 476(7358): 63-8.
  2. Guo  Z,  Dose  M,  Kovalovsky D,  Chang R, O'Neil J,
Look AT, et al. Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation. Blood 2007; 109(12): 5463-72.
  1. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A 2006; 103(48): 18261-6.
  2. Allman D, Karnell FG, Punt JA, Bakkour S, Xu L, Myung P, et al. Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells. J Exp Med 2001; 194(1): 99-106.
  3. Ng OH, Erbilgin Y, Firtina S, Celkan T, Karakas Z, Aydogan G, et al. Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia. Blood Cancer J 2014; 4: e192.
  4. Tiemessen MM, Baert MR, Schonewille T, Brugman MH, Famili F, Salvatori DC, et al. The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas. PLoS Biol 2012; 10(11): e1001430.
  5. Yu S, Zhou X, Steinke FC, Liu C, Chen SC, Zagorodna O, et al. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 2012; 37(5): 813-26.
  6. Giambra V, Jenkins CE, Lam SH, Hoofd C, Belmonte M, Wang X, et al. Leukemia stem cells in T-ALL require active Hif1alpha and Wnt signaling. Blood 2015; 125(25): 3917-27.
  7. Kaneta Y, Kagami Y, Tsunoda T, Ohno R, Nakamura Y, Katagiri T. Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray. Int J Oncol 2003; 23(3): 681-91.
  8. Schurch C, Riether C, Matter MS, Tzankov A, Ochsenbein AF. CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression. J Clin Invest 2012; 122(2): 624-38.
  9. Mazieres J, You L, He B, Xu Z, Lee AY, Mikami I, et al. Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis. Oncogene 2005; 24(34): 5396-400.
  10. Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001; 194(11): 1639-47.
  11. Melo N, Hobday C, Dowsett M, Catovsky D, Matutes E, Morilla R, et al. Oestrogen receptor (ER) analysis in B-cell chronic lymphocytic leukemia: correlation of biochemical and immunocytochemical methods. Leuk Res 1990; 14(11-12): 949-52.
  12. Roman-Gomez J, Cordeu L, Agirre X, Jimenez-Velasco A, San Jose-Eneriz E, Garate L, et al. Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia. Blood 2007; 109(8): 3462-9.
  13. Roman-Gomez J,  Jimenez- Velasco   A,     Cordeu L,
Vilas-Zornoza A, San Jose-Eneriz E, Garate L, et al. WNT5A, a putative tumour suppressor of lymphoid malignancies, is inactivated by aberrant methylation in acute lymphoblastic leukaemia. Eur J Cancer 2007; 43(18): 2736-46.
  1. Simon M, Grandage VL, Linch DC, Khwaja A. Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia. Oncogene 2005; 24(14): 2410-20.
  2. Wang L, You LS, Ni WM, Ma QL, Tong Y, Mao LP, et al. β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia. Leuk Res 2013; 37(10): 1329-40.
  3. Metzeler KH, Heilmeier B, Edmaier KE, Rawat VP, Dufour A, Dohner K, et al. High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia. Blood 2012; 120(10): 2118-26.
  4. Fu Y, Zhu H, Wu W, Xu J, Chen T, Xu B, et al. Clinical significance of lymphoid enhancer-binding factor 1 expression in acute myeloid leukemia. Leuk Lymphoma 2014; 55(2): 371-7.
  5. Zhang B, Li M, McDonald T, Holyoake TL, Moon RT, Campana D, et al. Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt-beta-catenin signaling. Blood 2013; 121(10): 1824-38.
  6. Dorfman DM, Greisman HA, Shahsafaei A. Loss of expression of the WNT/beta-catenin-signaling pathway transcription factors lymphoid enhancer factor-1 (LEF-1) and T cell factor-1 (TCF-1) in a subset of peripheral T cell lymphomas. Am J Pathol 2003; 162(5): 1539-44.
 
 
 
 


 
 
 
 
Sci J Iran Blood Transfus Organ 2018; 15(2): 149-164
Review  Article
 

 

The role of Wnt/β-catenin signaling pathway
in blood leukemias
 
Ghari M.1, Fathi E.1, Farahzadi R.2
 
 
 
1Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
2Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
 
 
 
Abstract
Background and Objectives
Wnt/β-catenin signaling pathway is one of the key cascades regulating development and stability of immune and blood cells, but its precise role is still controversial and is the subject of many studies. With activation of the canonical Wnt/β-catenin signaling pathway, β-catenin protein is imported into the nucleus and activates transcription of target genes including cyclin D1 and c-myc. The canonical Wnt ⁄ β-catenin signaling pathway is aberrantly activated in cancers, and it has therefore been investigated as a potential therapeutic target for the treatment of cancer. In this article, the significance of the canonical Wnt signaling pathway and its impact on blood leukemias development will be described, and how the change in the Wnt signaling pathway will cause any types of leukemia.
 
Materials and Methods
The data of the present article were obtained through the review of many papers published on the effect of Wnt / β-catenin signaling pathway on various types of leukemia.
 
Results
The review of various studies has shown that Wnt / β-catenin signaling pathway (canonical and non-canonical) is involved at a specific stage during pathogenesis of all types of hematologic malignancies.
 
Conclusions 
Since the Wnt/β-catenin signaling pathway plays an important role in the natural hematopoiesis and cellular malignancy in hematopoiesis system, evidently the changes in Wnt/ β-catenin signaling pathway provide therapeutic intervention opportunities, especially because of the significant increased level of Wnt/β-catenin signaling pathway in hematologic malignancies compared to other signaling pathways.
 
Key words: Wnt Signaling Pathway, Leukemia، Chronic Myeloid, Acute Myeloid Leukemia,
Acute Lymphoid Leukemia, Chronic Lymphocytic Leukemia
 
 
 
 
Received:  25 Nov 2017
Accepted: 30 Jan 2018
 
 

Correspondence: Fathi E., Specialist in Clinical Veterinary Pathology. Associate Professor of Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz.
Postal Code: 5166616471, Tabriz, Iran. Tel: (+9841) 13392351; Fax: (+9841) 13357834
E-mail:
ez.fathi@tabrizu.ac.ir
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA code


XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Ghari M, Fathi E, Farahzadi R. The role of Wnt/β-catenin signaling pathway in blood leukemias . Sci J Iran Blood Transfus Organ. 2018; 15 (2) :149-164
URL: http://bloodjournal.ir/article-1-1156-en.html


Volume 15, Issue 2 (Summer 2018) Back to browse issues page
فصلنامه پژوهشی خون Scientific Journal of Iran Blood Transfus Organ
The Scientific Journal of Iranian Blood Transfusion Organization - Copyright 2006 by IBTO
Persian site map - English site map - Created in 0.06 seconds with 32 queries by YEKTAWEB 3742