L-Asparaginase - Perspectives On The Mechanisms Of Action And Resistance

    Authors

    R. Chakrabarti;S. M. Schuster

    Comments

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    Abbreviated Journal Title

    Int. J. Pediatr. Hematol-Oncol.

    Keywords

    L-asparaginase; asparagine; asparagine synthetase; resistance; chemical; modification; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLI-L-ASPARAGINASE; CANCER STUDY-GROUP; ACUTE LYMPHOCYTIC-LEUKEMIA; MOUSE LYMPHOMA-CELLS; ESCHERICHIA-COLI; CHILDRENS CANCER; NITROGEN TRANSFER; CRYSTAL-STRUCTURE; DNA METHYLATION; Oncology; Hematology; Pediatrics

    Abstract

    L-Asparaginase, the enzyme that hydrolyzes asparagine to yield aspartic acid and ammonia, is isolated from various bacterial sources and is an effective and well-accepted chemotherapeutic agent, especially in the treatment of pediatric acute lymphoblastic leukemia. The enzyme works by depleting the tumor of its source of asparagine from the circulation, as tumors specifically of lymphoid origin are incapable of intracellular asparagine synthesis and are L-asparaginase-sensitive upon presentation. Despite its effectiveness, however, the use of L-asparaginase as a chemotherapeutic agent is somewhat limited because of its toxicity and spontaneous acquisition of resistance to this enzyme by the tumor cells. Numerous side effects of L-asparaginase treatment have been reported and present a clinical challenge. Resistance to L-asparaginase occurs often and is highly correlated with an increase in the cellular production of asparagine synthetase, the enzyme responsible for asparagine biosynthesis. inactivation of asparagine synthetase in resistant tumor cells renders them sensitive to L-asparaginase treatment. Different strategies to inhibit intracellular asparagine synthetase are being used to overcome L-asparaginase resistance. Additional resistance can occur due to immunologic reactions to the foreign protein. Strategies of chemical modification of L-asparaginase have been used successfully to diminish the immunogenicity of the enzyme and enhance its utility in treatment of acute lymphoblastic leukemia.

    Journal Title

    International Journal of Pediatric Hematology/Oncology

    Volume

    4

    Issue/Number

    6

    Publication Date

    1-1-1997

    Document Type

    Review

    Language

    English

    First Page

    597

    Last Page

    611

    WOS Identifier

    WOS:000072440100008

    ISSN

    1070-2903

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