Assessment of Serum Tryptase Activity Among Acute and Chronic Myeloid Leukemia Patients Visiting Hematology-Oncology Clinic at TikurAnbessa Specialized Hospital, and Comparison with Healthy Controls
Cancer Research Journal
Volume 6, Issue 1, March 2018, Pages: 26-37
Received: Jan. 3, 2018;
Accepted: Jan. 29, 2018;
Published: Mar. 5, 2018
Views 803 Downloads 31
Endriyas Kelta, Department of Biomedical Sciences, Jimma University, Jimma, Ethiopia
Frank Ashall, Department of Biochemistry, Addis Ababa University, Addis Ababa, Ethiopia
Abdulaziz Abubeker, Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia
Tryptase is a serine protease that is expressed in leukemic cells of chronic myeloid leukemia (CML) patients and in blasts of acute myeloid leukemia (AML) patients. Tryptase may be useful for diagnosis, assessment of severity of disease (leukemic cell burden), monitoring minimal residual disease and prognosis of AML and CML patients. The main objective of this study was to assess the serum levels of tryptase activity among CML and AML patients and to compare the serum levels of tryptase activity of acute and chronic myeloid leukemia patients with each other and with those of healthy controls. To meet this objective, a hospital-based comparative cross-sectional study was conducted among CML and AML patients from February 2016 up to December 2016. Serum samples were obtained from 24 AML, 60 CML and 35 healthy controls. Fluorogenic assays for serum tryptase activity using aminomethylcoumarin (AMC) peptide derivative were carried out. Statistical analysis was done by using SPSS version 20. Descriptive statistics, Paired Samples T-test, Wilcoxon Signed Rank test and Spearman’s rho test were used to investigate any correlation among different parameters. The minimum level of statistical significance was set at p-value <0.05. Accordingly, the mean and median serum levels of tryptase activity were significantly higher in patients with AML and CML than in the healthy controls (P-value < 0.05). CML patients in chronic phase (CP) and secondary AML patients had significantly higher mean and median serum levels of tryptase activity than CML patients in accelerated/blast phase (AP/BP) and de novo AML patients (p-value < 0.05). These elevated mean and median levels of serum tryptase activities were due to a subset of individuals with elevated serum tryptase levels (41.7 % of AML & 30 % of CML); the remaining leukemic individuals (58.3 % AML & 70 % of CML) had normal serum levels of tryptase activity. Finally, it was concluded that the serum tryptase level might be a useful diagnostic and prognostic marker in a subset of patients with CML and AML. However, further studies that incorporate other protocols such as tryptase immunoassay are warranted to exclude contaminant non-tryptase proteases from the serum samples.
Assessment of Serum Tryptase Activity Among Acute and Chronic Myeloid Leukemia Patients Visiting Hematology-Oncology Clinic at TikurAnbessa Specialized Hospital, and Comparison with Healthy Controls, Cancer Research Journal.
Vol. 6, No. 1,
2018, pp. 26-37.
American Cancer Society (2015). Leukemia–Acute Myeloid (Myelogenous). Cancer Facts & Figures. Atlanta, Ga: American Cancer Society; 1-60.
Ammendola M., Leporini C., Marech I.,Gadaleta D. C., Scognamillo G.,Sacco R., Sammarco G.,De Sarro G., Russo E., and Ranieri G. (2014a). Targeting Mast Cells Tryptase in Tumor Microenvironment:A Potential Antiangiogenetic Strategy.Review Article: BioMed Research International, http://dx.doi.org/10.1155/2014/154702; 1-16.
Ammendola M., Sacco R., Sammarco G., Donato G., Montemurro S., Ruggieri E., Patruno R., Marech I., Cariello M.,Vacca A., Gadaleta D. C. and Ranieri G. (2014b). Correlation between Serum Tryptase, Mast Cells Positive to Tryptase and Microvascular Density in Colo-Rectal Cancer Patients: Possible Biological-Clinical Significance. PLoS ONE/ www.plosone.org; 9(6): e99512.
Cairoli R., Ripamonti B. C., Beghini A., Granata S., Grillo G., Brioschi M., Nadali G., Viola A., Cattaneo C., Inropido L., Ravelli E., Bertani G., Pezzetti L., Nichelatti M., Marocchi A., Rossi G., Pizzolo G., Ferrara F., Nosari M. A., Morra E. (2009). Total serum tryptase: A predictive marker for KIT mutation in acute myeloid leukemia. Leukemia Research; 33: 1282–1284.
Caughey H.G., Raymond W. W., Blount L. J., Hau T. W.,Pallaoro M., Wolters J. P., and Verghese M. G. (2000). Characterization of Human g-Tryptases, Novel Members ofthe Chromosome 16p Mast Cell Tryptase and Prostasin GeneFamilies. The Journal of Immunology; 164: 6566–6575.
Davies J.N.P. (1973). Childhood tumors. In: Templeton, A.C., ed., Tumors in a TropicalCountry (Recent Results in Cancer Research No. 41), Berlin, Springer Verlag.
Gocek E. and Marcinkowska E. (2011). Differentiation Therapy of Acute Myeloid Leukemia. Review; 3: 2402-2420.
Guo Y., Wu Q., Ni B., Mou Z., Jiang Q., Cao Y., Dong H. and Wu Y. (2013). Tryptase is a candidate autoantigen in rheumatoid arthritis. The Journal of cells, molecules,systems and technologies; 142, 67–77.
Ibrahim E. and Osman I. (2011). Myeloid Leukemia: A Molecular Focus on Etiology and Risk Within Africa, Myeloid Leukemia - Basic Mechanisms of Leukemogenesis, Steffen Koschmieder (Ed.), ISBN: 978-953-307-789-5. In Tech, Available from: http://www.intechopen.com/books/myeloid-leukemia.
Itoh Y., Sendo T., and Oishi R. (2005). Physiology and Pathophysiology of Proteinase Activated Receptors (PARs): Role of Tryptase/PAR-2 in Vascular Endothelial Barrier Function.Journal of Pharmacological Sciences; 97:14–19.
Junior A. D., Santana C. A.,Marcelino da Silva Z. E., Oliver C., and Jamur C. M.(2015). The Role of Mast Cell Specific Chymasesand Tryptases in Tumor Angiogenesis. Review Article: BioMed Research International;1-13.
Kasili E. G. (1990). Childhood Leukemia: Is it a Problem in Tropical Africa? Leukemia &Lymphoma, Vol. 1, No. 3-4, 187-193.
King T.G.(2014). Serum Tryptase: Reference range, Interpretation, collection and panel. Madcaps Drugs and Disease;1-10.
Lockwood W. (2015). Leukemia: AML, CML, ALL and CLL. www.RN.ORG. ©2015 RN.ORG®, S.A..RN.ORG®, LLC. ISBN: 678-693-1-32.
Marech I., Ammendola M., Gadaleta C., Zizzo N., Oakley C., Gadaleta D. C., and Ranieri G. (2014). Possible biological and translational significance of mastcells density in colorectal cancer. World JGastroenterol; 20(27): 8910-8920.
Mori S.,Itoh Y., Shinohata R., Sendo T., Oishi R., and Nishibori M. (2003). Nafamostat Mesilate Is an Extremely Potent Inhibitor of Human Tryptase. Journal of Pharmacological Sciences; 92:420–23.
National Cancer Institute, (2001). Genes and Disease: blood and lymph diseases. Available at: Cancer.gov (http://www.cancer.gov/cancerinfo/wyntk/leukemia.)
Nwannadi, O. Alao, G. Bazuaye, M. Nwagu & M. Borke (2011). Clinical and Laboratory Characteristics of Patients with Leukaemia in South-South Nigeria. The Internet Journal of Oncology; 7 (2).
Obama, M.T., L. Zekeng, P.K. Ketchiozo, M.B. Owono, B.T. Kouam, & J. Mbede. (1995).Childhood leukemia is still a deadly disease in Yaounde, Cameroon: a report of 14cases. Pediatr Hematol Oncol 12: 301-304.
Roboz J.G. (2011). Novel Approaches to the Treatment of Acute MyeloidLeukemia.Acute Myeloid Leukemia in the Age of Genomics; 43-50.
Sendo T.,Itoh Y., Goromaru T., Sumimura T., Saito M., Aki K., Yano T., and Oishi R. (2003). A potent tryptase inhibitor nafamostat mesilate dramatically suppressed pulmonary dysfunction induced in rats by a radiographic contrast medium. British Journal of Pharmacology; 138: 959-967.
Shamebo M. (1990). Leukaemia in adult Ethiopians. Ethiop Med J, 28(1): 31-7.
Sirvent A., González C., Enríquez R., Fernández J., Millán I., Barber X. and Amorós F. (2010). Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease JNEPHROL; 23(03): 282-290.
Sommerhoff P. C., Bode W., Pereira B. J., Stubbs T.M., Rzebecher J., Piechottka P. G., Matschiner G., and Bergner A. (1999).The structure of the human βII-tryptase tetramer: Fo (u) r betteror worse. Proc. Natl. Acad. Sci. USA; 96: 10984–10991.
Sperr R. W., Mitterbauer M., Mitterbauer G., Kundi M., Jager U., Lechner K., and Valent P. (2005). Quantization of Minimal Residual Disease in Acute Myeloid Leukemia by Tryptase Monitoring Identifies a Group of Patients with a High Risk of Relapse. Clin Cancer Res. Imaging, Diagnosis, Prognosis; 11(18): 6536-43.
Sperr R. W., Pfeiffer T., Hoermann G., Herndlhofer S., Mannhalter C.,Kundi M., and Valent P. (2015a).Serum-tryptase at diagnosis: a novel biomarker improving prognostication in Ph+ CML. Am J Cancer Res; 5(1):354-362.
Sperr R.W., El-Samahi A., Kundi M., Girschikofsky M., Winkler S., Lutz D., Endler G., Rumpold H., Agis H., Sillaber C., Jager U. and Valent P.(2009). Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology. European Journal of Clinical investigation; 39(10): 914-923.
Sperr R.W., Jordan H.J., Baghestanian M., Kiener P. H., Samorapoompichit P.,HauswirthA. H., Schernthaner H.G., Chott A., Natter S., Kraft D., Valenta R., Schwartz B. L., Geissler K., Lechner K., and Valent P. (2015b). Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. Neoplasia: www.bloodjournal.org; 98(7): 2200-2209.
Strouch M., Cheon E., Salabat M., KrantzS., Gounaris E., Melstrom L., Dangi-Garimella S., WangE.,Munshi H., KhazaieK., and BentremD. (2011). Crosstalk between mast cells and pancreatic cancer cellscontributes to pancreatic tumor progression. Clin Cancer Res.; 16(8): 2257–2265. doi:10.1158/1078-0432.CCR-09-1230.
Wysocka M. and Lesner A. (2013). Future of Protease Activity Assays. Current Pharmaceutical Design; 19(6): 1062-1067.
Zhang G. (2006). Protease Assays. Assay Guidance Manual; NBK9: pp. 1-14.