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Abstract
Background: Soluble FasL (sFasL) generating from Membrane-bound FasL (mFasL) cleaved by matrix metalloproteinases (MMPs). sFasL inhibits the apoptotic and inflammatory activity of mFasL because of sFasL competes with the mFasL and binds to Fas. To evaluate serum soluble Fas ligand (sFasL) level in patients with chronic myeloid leukemia.
Materials and Method: Serum levels of sFasL were measured by ELISA method after venous blood was collected from 56 CML patients (newly diagnosed and optimally treated) and 28 healthy subjects as control group.
Results: There were no significant increases in serum sFasL patient compared to healthy control with P=0.07. When the mean sFasL concentration was obviously highest in newly diagnosed (216.9pg/ml) followed by healthy control (152.5pg/ml) and lowest in optimally treated (147.7 pg/ml).
Conclusion: Production of sFasL in tumor patients may be a key mechanism to inhibit Fas-mediated apoptosis.
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References
- Shallis RM.; Wang R.; Davidoff A.; Ma X.; Podoltsev NA. & Zeidan AM. (2020). Epidemiology of the classical myeloproliferative neoplasms: the four corners of an expansive and complex map. Blood Rev., 42:100706. doi:10.1016/j.blre.2020.100706
- Nannya Y.; Imai Y.; Hangaishi A. & Kurokawa M. (2008). An Extended Mathematical Model of Pathophysiology and Response to Treatment in Chronic Myelogenous Leukemia. Blood,112 (11): 4220.
- How J.; Venkataraman V.& Hobbs G.S. (2021).Blast and accelerated phase CML: room for improvement. Hematology Am Soc Hematol Educ Program, 2021(1): 122–128. doi: https://doi.org/10.1182/hematology.2021000240
- Kang ZJ.; Liu YF.; Xu LZ.; Long ZJ.; Huang D.; Yang Y.; Liu B.; Feng JX.; Pan YJ.; Yan JS. & Liu Q.(2016). The Philadelphia chromosome in leukemogenesis. Chinese Journal of Cancer, 35:48.
- DOI: 10.1186/s40880-016-0108-0
- Granatowicz A.; Piatek CI.; Moschiano E.; El-Hemaidi I.; Armitage JD. & Akhtari M. (2015). An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians. Korean Journal of Family Medicine, 36(5): 197– 202. doi: 10.4082/kjfm.2015.36.5.197.
- De la Fuente J.; Baruchel A.; Biondi A.; de Bont E.; Dresse MF.; Suttorp M. & Millot F. (2014). Chronic Myeloid Leukaemia Committee. Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years. British Journal of Haematology, 167(1):3347.doi:10.1111/bjh.12977.
- Liu W.; Ramagopal U.; Cheng H.; Bonanno JB.; Toro R.; Bhosle R.; Zhan C.; Almo SC. (2016). Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure, 24 (11): 2016-2023. DOI: https://doi.org/10.1016/j.str.2016.09.009.
- Kim WU.; Kwok SK.; Hong KH.; Yoo SA.; Kong JS.; Choe J. & Cho CS. (2007). Soluble Fas ligand inhibits angiogenesis in rheumatoid arthritis. Arthritis Research &Therapy, 9(2): R42.
- Dockrell D.H. (2003). The multiple roles of Fas ligand in the pathogenesis of infectious diseases. Clinical Microbiology and Infection, 9(8): 766-779. https://doi.org/10.1046/j.1469-0691.2003.00669.x.
- Jeong D.; Kim HS.; Kim HY.; Kang MJ.; Jung H.;Oh Y.; Kim D.; Koh J.; Cho S.; Jeon YK.; Lee EB.; Lee SH.; Shin E.; Kim HM.; Yi EC. & Chung DH. (2021).Soluble Fas ligand drives autoantibody-induced arthritis by binding to DR5/TRAIL-R2. eLife, 10:e48840.https://doi.org/10.7554/eLife.48840
- Krishnan A.; Fei F.; Jones A.; Busto P.; Marshak-Rothstein A.; Ksander BR. & Gregory-Ksander M. (2016). Overexpression of Soluble Fas Ligand following Adeno-Associated Virus Gene Therapy Prevents Retinal Ganglion Cell Death in Chronic and Acute Murine Models of Glaucoma. The Journal of Immunology, 197 (12) 4626-4638. DOI: 10.4049/jimmunol.1601488
- Yamada A.; Arakaki R.; Saito M.; Kudo Y. & Ishimaru N. (2017). Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Frontiers in Immunology, 8:403. 8doi: 10.3389/fimmu.2017.00403
- Nada HR. (2016). Fas receptor. Global Dermatology, 3: DOI: 10.15761/GOD.1000167.
- Holler N.; Tardivel A.; Kovacsovics-Bankowski M.; Hertig S.; Gaide O.; Martinon F.; Tinel A.; Deperthes D.; Calderara S.; Schulthess T.; Engel J.; Schneider P. & Tschopp J. (2003). Two Adjacent Trimeric Fas Ligands Are Required for Fas Signaling and Formation of a Death-Inducing Signaling Complex. Molecular and Cellular Biology, 23(4):1428_1440. Doi: 10.1128/MCB.23.4.1428-1440.2003
- SAS. (2012) . Statistical Analysis System, User's Guide. Statistical. Version 9.1th ed. SAS. Inst. Inc. Cary. N.C. USA.
- Tanaka M.; Suda T.; Haze K.; Nakamura N.; Sato K.; Kimura F.; Motoyoshi K.; Mizuki M.; Tagawa S.; Ohga S.; Hatake K.; Drummond AH. & Nagata S. (1996). Fas ligand in human serum. Nature Medicine, 2(3): 317–322.
- De Maria R.; Testa U.; Luchetti L.; Zeuner A.; Stassi G.; Pelosi E.; Riccioni R.; Felli N.; Samoggia P. &Peschle C. (1999). Apoptotic Role of Fas/Fas Ligand System in the Regulation of Erythropoiesis. Blood, 93(3): 796-803.
- Shimizu M.; Kondo M.; Ito Y.; Kume H.; Suzuki R. &Yamaki K. (2005). Soluble Fas and Fas ligand provide new information on metastasis and response to chemotherapy in SCLC patients. Cancer Detect Prev., 29(2):175-180.
- Bellone G.; Smirne C.; Carbone A.; Mareschi K.; Dughera L.; Farina EC.; Alabiso O.; Valente G.; Emanuelli G. & Rodeck U. (2000). Production and pro-apoptotic activity of soluble CD95 ligand in pancreatic carcinoma. Clinical Cancer Research,6(6):2448-2455.
- O’Connell J.; O’Sullivan GC.; Collins JK. & Shanahan F. (1996). The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. The Journal of experimental medicine, 184(3):1075–1082.
- Gratas C.; Tohma Y.; Barnas C.; Taniere P.; Hainaut P. & Ohgaki H. (1998). Upregulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in human esophageal cancer. Cancer Research, 58(10): 2057–2062.
- Kozlowski M.; Kowalczuk O.; Sulewska A.; Dziegielewski P.; Lapuc G.; Laudanski W.; Niklinska W.; Chyczewski L.; Niklinski J. & Laudanski J. (2007). Serum soluble Fas ligand (sFasL) in patients with primary squamous cell carcinoma of the esophagus. Folia Histochemica et Cytobiologica, 45(3):199-204.
- Lim S. (2002). Expression of Fas ligand and sFas ligand in human gastric adenocarcinomas. Oncology Reports, 9(1): 103-107.
- Kanda Y.; Chiba S.; Tanaka Y.; Kami M.; Saito M.;Izutsu K.;Asai T.; Yuji K.; Ogawa S.; Honda H.;Mitani K.;Usuki K.; Urabe A.; Shirakawa K.; Yatomi T.; Nakamura N.; Yazaki Y. & Hirai H. (1999). Increased Serum Soluble Fas Ligand Associated with Recurrent B-Cell Non-Hodgkin's Lymphoma after Autologous Peripheral Blood Stem Cell Transplantation. Leukemia & Lymphoma, 34(5-6): 625-628. https://doi.org/10.3109/10428199909058494
- Urbaniak-Kujda D.; Jaźwiec B.; Tomaszewska-Toporska B.; Wołowiec D.; Kapelko-Słowik K. & Kuliczkowski K. (2002). Expression of Fas receptor and soluble Fas ligand (sFasL) concentration in acute leukemia. Polskie Archiwum Medycyny Wewnetrznej, 108(3): 873-878.
- Murakami M.; Sasaki T.; Miyata H.; Yamasaki S; KuwaharaK. & Chayama K. (2004). Fas and Fas ligand: Expression and soluble circulating levels in bile duct carcinoma. Oncology Reports, 11(6): 1183-1186.
- Jiang S.; Moriarty-Craige SE.; Li C.; Lynn MJ.; Cai J.; Jones DP. & Sternberg P. (2008). Associations of plasma-soluble fas ligand with aging and age-related macular degeneration. Investigative Ophthalmology & Visual Science, 49(4): 1345-1349.