| Peer-Reviewed

Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study

Received: 25 December 2018     Accepted: 7 February 2019     Published: 25 February 2019
Views:       Downloads:
Abstract

Proteosome, composed of 19S and 20S subunits, is vital for AML and CML cell cycling, proliferation, adhesion and as a means to by-pass apoptosis through three distinguishable proteolytic activities. Chymotrypsin-like (CT-L) activity is rate limiting and a well-established therapeutic strategy for AML and CML cells, by proteosome inhibitors than the other two proteolytic activities: trypsin-like activities and caspase-like activities. As the main objective of the study, the serum levels of Chymotrypsin-like activity was assessed among chronic and acute myeloid leukemia patients, and compared among each other and with those of healthy controls. 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 presumed healthy controls. Fluorogenic assays for serum chymotrypsin-like activity using aminomethylcoumarin (AMC) peptide derivatives 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. The mean and median serum levels of Chymotrypsin-like activity were significantly higher in patients with CML and AML 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 Chymotrypsin-like activity than CML patients in accelerated/blast phase (AP/BP) and de novo AML patients (p-value < 0.05). As a conclusion, the serum Chymotrypsin-like activity level might be a useful diagnostic test, and may be used as prognostic test particularly in a subset of CML patientsin chronic phase (CP) and Secondary AML patients. However, further studies that incorporate other protocols such as chymotrypsin-like activity enzyme-immunoassay with large scaled study population are warranted to decide on prognostic and diagnostic role of the enzyme more accurately.

Published in American Journal of Life Sciences (Volume 7, Issue 1)
DOI 10.11648/j.ajls.20190701.12
Page(s) 5-11
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

CML, AML, Serum Chymotrypsin-Like Activity

References
[1] Nicholas B. H., Francesca P., Bin Z., Lisa C., Su C., Syed M. A. K., Elaine K. A., 1 Heather G. J., Alexandra E. I., Ravi B., Tessa L. H. Bortezomib induces apoptosis in primitive chronic myeloid leukemia cells including LTC-IC and NOD/SCID repopulating cells (2010). The American Society of Hematology; BLOOD, VOLUME 115 (11):2241-2251.
[2] Peter T., Alexandre D., Kai C., Heather R. K., Zarina B., Weiwen Y., Prathapan T., Mairead R., Guillaume K., Aviad T., Sandro S., Luke W., John L. M., Irene M. G., Susan L. Inhibition of mitochondrial ferredoxin 1 (FDX1) prevents adaptation to proteotoxic stress (2018). doi: http://dx.doi.org/10.1101/288365.
[3] Marion P., Sandrine B., Ruoping T., Christian B., Daniel D., Brigitte B. p7OS6 kinase is a target of the novel proteasome inhibitor 3,3’-diamino-4’-methoxyflavone during apoptosis in human myeloid tumor cells (2013). Elsevier; Biochimicaet Biophysica Acta 1833:1316-1328.
[4] Hassan F., Asmaa Q., Laurent H., Said E., Souad A. Serum and subcellular proteasome in Moroccan patients reached hematologicalmalignancies (2015). Int J Med Health Sci.; Vol-4 (Issue-2):217-224.
[5] Camilla S., Anne P. D., Kimberley H., Elisabeth E., Anita R., James B. L., Bjørn T. G., Øystein B. The proteasome inhibitors bortezomib and PR-171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemiacells (2007). British Journal of Haematology, 136, 814-828.
[6] Claudia P. M., Kechen B., Melanie E. D., David J. M., Mark M., Michael P., Joya C. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells (2007). The American Society of Hematology; BLOOD, VOLUME 110 (1): 1-11.
[7] Selin E., Miriş D., Yusuf Ö. Comparison of antiproliferative and apoptotic effects of a novel proteasome inhibitor MLN2238 with bortezomib on K562 chronic myeloid leukemia cells (2015). Journal of Immunopharmacology And Immunotoxicology; p1-19.
[8] Piotrowski Z., Myśliwiec P., Gryko M., Ostrowska H., Baltaziak M. Chymotrypsin-like activity in rat tissues in experimental acute pancreatitis (2003). Roczniki Akademii Medycznej w Białymstoku • Vol. 48:61-65.
[9] Di C., Kristin R. L., Marina S. C., Q Ping D. Inhibition of proteasome activity by the dietary flavonoid apigeninis associated with growth inhibition in cultured breast cancer cellsand xenografts (2007). Breast Cancer Research; Vol 9 (6):1-8. Doi: 10.1186/bcr1797.
[10] Evelyn W. W., Benedikt M. K., Anna B., Benjamin F. C., Matthew B., Hidde L. P., Rickard G. Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity (2000). PNAS; Vol. 97 (18): 9990–9995.
[11] Lesner A. and Wysocka M. (2013). Future of Protease Activity Assays. Current Pharmaceutical Design; 19 (6): 1062-1067.
[12] Chott A., Natter S., Sperr R. W., Jordan H. J., Baghestanian M., Kiener P. H., Samorapoompichit P., Hauswirth A. H., Schernthaner H. G., 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.
[13] Santana C. A., Jamur C. M., Junior A. D., Marcelino da Silva Z. E., Oliver C. (2015). The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis. Review Article: Bio Med Research International; 1-13.
[14] Mou Z., Jiang Q., Guo Y., Wu Q., Ni B., 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.
[15] Beghini A., Granata S., Grillo G., Brioschi M., Nadali G., Viola A., Cattaneo C., Inropido L., Ravelli E., Bertani G., Cairoli R., Ripamonti B. C., 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.
Cite This Article
  • APA Style

    Endriyas Kelta Wabalo, Abdulaziz Abubeker, Chala Kenenisa Edae, Belay Zawdie. (2019). Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study. American Journal of Life Sciences, 7(1), 5-11. https://doi.org/10.11648/j.ajls.20190701.12

    Copy | Download

    ACS Style

    Endriyas Kelta Wabalo; Abdulaziz Abubeker; Chala Kenenisa Edae; Belay Zawdie. Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study. Am. J. Life Sci. 2019, 7(1), 5-11. doi: 10.11648/j.ajls.20190701.12

    Copy | Download

    AMA Style

    Endriyas Kelta Wabalo, Abdulaziz Abubeker, Chala Kenenisa Edae, Belay Zawdie. Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study. Am J Life Sci. 2019;7(1):5-11. doi: 10.11648/j.ajls.20190701.12

    Copy | Download

  • @article{10.11648/j.ajls.20190701.12,
      author = {Endriyas Kelta Wabalo and Abdulaziz Abubeker and Chala Kenenisa Edae and Belay Zawdie},
      title = {Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study},
      journal = {American Journal of Life Sciences},
      volume = {7},
      number = {1},
      pages = {5-11},
      doi = {10.11648/j.ajls.20190701.12},
      url = {https://doi.org/10.11648/j.ajls.20190701.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.20190701.12},
      abstract = {Proteosome, composed of 19S and 20S subunits, is vital for AML and CML cell cycling, proliferation, adhesion and as a means to by-pass apoptosis through three distinguishable proteolytic activities. Chymotrypsin-like (CT-L) activity is rate limiting and a well-established therapeutic strategy for AML and CML cells, by proteosome inhibitors than the other two proteolytic activities: trypsin-like activities and caspase-like activities. As the main objective of the study, the serum levels of Chymotrypsin-like activity was assessed among chronic and acute myeloid leukemia patients, and compared among each other and with those of healthy controls. 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 presumed healthy controls. Fluorogenic assays for serum chymotrypsin-like activity using aminomethylcoumarin (AMC) peptide derivatives 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. The mean and median serum levels of Chymotrypsin-like activity were significantly higher in patients with CML and AML than in the healthy controls (P-value de novo AML patients (p-value < 0.05). As a conclusion, the serum Chymotrypsin-like activity level might be a useful diagnostic test, and may be used as prognostic test particularly in a subset of CML patientsin chronic phase (CP) and Secondary AML patients. However, further studies that incorporate other protocols such as chymotrypsin-like activity enzyme-immunoassay with large scaled study population are warranted to decide on prognostic and diagnostic role of the enzyme more accurately.},
     year = {2019}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Serum Chymotrypsin-Like Activity on Digestion of Ala-Ala-AMC as a Substrate, Among CML and AML Patients at TASH, Addis Ababa Ethiopia: A Comparative Cross-Sectional Study
    AU  - Endriyas Kelta Wabalo
    AU  - Abdulaziz Abubeker
    AU  - Chala Kenenisa Edae
    AU  - Belay Zawdie
    Y1  - 2019/02/25
    PY  - 2019
    N1  - https://doi.org/10.11648/j.ajls.20190701.12
    DO  - 10.11648/j.ajls.20190701.12
    T2  - American Journal of Life Sciences
    JF  - American Journal of Life Sciences
    JO  - American Journal of Life Sciences
    SP  - 5
    EP  - 11
    PB  - Science Publishing Group
    SN  - 2328-5737
    UR  - https://doi.org/10.11648/j.ajls.20190701.12
    AB  - Proteosome, composed of 19S and 20S subunits, is vital for AML and CML cell cycling, proliferation, adhesion and as a means to by-pass apoptosis through three distinguishable proteolytic activities. Chymotrypsin-like (CT-L) activity is rate limiting and a well-established therapeutic strategy for AML and CML cells, by proteosome inhibitors than the other two proteolytic activities: trypsin-like activities and caspase-like activities. As the main objective of the study, the serum levels of Chymotrypsin-like activity was assessed among chronic and acute myeloid leukemia patients, and compared among each other and with those of healthy controls. 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 presumed healthy controls. Fluorogenic assays for serum chymotrypsin-like activity using aminomethylcoumarin (AMC) peptide derivatives 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. The mean and median serum levels of Chymotrypsin-like activity were significantly higher in patients with CML and AML than in the healthy controls (P-value de novo AML patients (p-value < 0.05). As a conclusion, the serum Chymotrypsin-like activity level might be a useful diagnostic test, and may be used as prognostic test particularly in a subset of CML patientsin chronic phase (CP) and Secondary AML patients. However, further studies that incorporate other protocols such as chymotrypsin-like activity enzyme-immunoassay with large scaled study population are warranted to decide on prognostic and diagnostic role of the enzyme more accurately.
    VL  - 7
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Biomedical Sciences, Jimma University, Jimma, Ethiopia

  • Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia

  • Department of Biomedical Sciences, Jimma University, Jimma, Ethiopia

  • Department of Biomedical Sciences, Jimma University, Jimma, Ethiopia

  • Sections