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.
Highlights
Leukemia cells, either Acute myeloid leukemia (AML) or Chronic myeloid leukemia (CML) cells, bypasses growth arrest, terminal differentiation or apoptosis in response to appropriate environmental stimuli
We proposed to study the variations of serum chymotrypsin-like activity in Ethiopian patients with CML and AML as well as in between AML and CML patients and healthy controls
It was found that the mean level of serum chymotrypsin-like activity was significantly lower in healthy controls than in CML patients and AML patients (Paired Samples T-test,% CI = 95, p-value = 0.00) (Table 1)
Summary
Either AML or CML cells, bypasses growth arrest, terminal differentiation or apoptosis in response to appropriate environmental stimuli. Proteasome, an intracellular organelle providing a targeted mechanism for protein degradation, composed of 19S and 20 S subunits in eukaryotes including human beings, and is vital for cancer cell (such as AML and CML cells), cycling, adhesion, proliferation, and apoptosis via chymotrypsin-like (CT-L) catalytic specificities [1]. Proteasome-mediated protein degradation via chymotrypsin-like (CT-L) activity is a key regulator of protein homeostasis or is rate limiting and a well-established therapeutic strategy for cancer cell (such as AML and CML cells), by proteosome inhibitors [2, 4, 6]. Literatures on natural compounds indicate that flavonoids and isoflavones down regulate the expression of anti-apoptotic proteins and inhibit proteasome mediated protein degradation via chymotrypsin-like (CT-L) activity and bring their antitumeric activity [3, 5]
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