4.5 Review

A systematic review of recent trends in research on therapeutically significant l-asparaginase and acute lymphoblastic leukemia

Journal

MOLECULAR BIOLOGY REPORTS
Volume 49, Issue 12, Pages 11281-11287

Publisher

SPRINGER
DOI: 10.1007/s11033-022-07688-4

Keywords

l-asparaginase; Acute lymphoblastic leukemia; Acrylamide; Immobilization; Machine learning; CRISPR-Cas9

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L-Asparaginases are widely used in the treatment of Acute Lymphoblastic Leukemia (ALL) and reducing acrylamide in the food industry. However, the enzyme's side effects and the risk of acrylamide-induced carcinogenesis limit its application. Enzyme immobilization and gene editing techniques are important approaches to improve its efficacy.
l-asparaginases are mostly obtained from bacterial sources for their application in the therapy and food industry. Bacterial l-asparaginases are employed in the treatment of Acute Lymphoblastic Leukemia (ALL) and its subtypes, a type of blood and bone marrow cancer that results in the overproduction of immature blood cells. It also plays a role in the food industry in reducing the acrylamide formed during baking, roasting, and frying starchy foods. This importance of the enzyme makes it to be of constant interest to the researchers to isolate novel sources. Presently l-asparaginases from E. coli native and PEGylated form, Dickeya chrysanthemi (Erwinia chrysanthemi) are in the treatment regime. In therapy, the intrinsic glutaminase activity of the enzyme is a major drawback as the patients in treatment experience side effects like fever, skin rashes, anaphylaxis, pancreatitis, steatosis in the liver, and many complications. Its significance in the food industry in mitigating acrylamide is also a major reason. Acrylamide, a potent carcinogen was formed when treating starchy foods at higher temperatures. Acrylamide content in food was analyzed and pre-treatment was considered a valuable option. Immobilization of the enzyme is an advancing and promising technique in the effective delivery of the enzyme than in free form. The concept of machine learning by employing the Artificial Network and Genetic Algorithm has paved the way to optimize the production of l-asparaginase from its sources. Gene-editing tools are gaining momentum in the study of several diseases and this review focuses on the CRISPR-Cas9 gene-editing tool in ALL.

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