Screening for Alternative Sources of L-Asparaginase Used in Acute Lymphoblastic Leukaemia (All) Treatment: An In Silico Approach

Abstract

Acute Lymphoblastic Leukemia (ALL) is the most prevalent acute leukemia in children and it also represents a devastating disease when it occurs in adults. Within the United States, the incidence of ALL is estimated at 1.6 per 100 000 population and an estimated 6590 new cases were diagnosed in 2016 alone. The enzyme L-asparaginase (L-Asp) is being used for treatment of childhood acute lymphoblastic leukemia (ALL) for many years because of its unique pharmacological features and historically improved treatment outcomes. As Lasparaginase demonstrates relative substrate specificity and at the same time affects the glutamine metabolism, these may intensify adverse effects including hepatotoxicity, hemostatic disorders and hyperglycemia. That’s why alternative L-asparaginase sources are crying needed to tackle the present drawbacks of commercially available L-asparaginase (For example, PEG-asparaginase from Erwiniachry santhemi). The present study planned to suggest an alternative source of L-asparaginase for ALL treatment by in silico analysis, mostly for child patient. The study included phylogenetic tree construction, physiochemical properties analysis, the secondary structure screening and three-dimensional structure prediction of proposed Lasparaginase. After phylogeny analysis and in slico screening of physiochemical and secondary properties, homology modeling of L-asparaginase Shigella boydii (WP_000513786.1) was uggested as the best alternative option for ALL treatment rather than commercially available L-asparaginase sources.