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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schlaifer, D. Articles by Myers, C. E. Search for Related Content PubMed PubMed Citation Articles by Schlaifer, D. Articles by Myers, C. E. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Myeloperoxidase: an enzyme involved in intrinsic vincristine resistance in human myeloblastic leukemia D Schlaifer, MR Cooper, M Attal, AO Sartor, JB Trepel, G Laurent and CE Myers Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. One of the differences between acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) is their sensitivity to vincristine. Although vincristine plays an important role in chemotherapeutic regimens for ALL, it does not possess clinically significant activity in AML. Horseradish peroxidase, a heme-centered peroxidase, oxidatively degrades Vinca derivatives and thereby abrogates their cytotoxic activity. This finding suggested that myeloperoxidase (MPO), a heme- centered peroxidase characteristically found in AML and not in ALL, might also degrade vincristine. We first examined the effects of MPO on vincristine in a cell-free system and demonstrated that this enzyme is capable of catalyzing vincristine's oxidative breakdown. We also observed that vincristine is more rapidly degraded in tissue culture by MPO-positive HL-60 cells than by a MPO-negative HL-60 subclone. The degree of MPO activity in these cell lines correlated in a positive manner with their degree of resistance to vincristine's cytotoxic activity. Moreover, the differential resistance to vincristine observed between these cell lines could be increased by increasing the concentration of H2O2 available to the enzyme. These data support the hypothesis that MPO-mediated oxidation of vincristine accounts in part for this drug's lack of activity in AML. Volume 81, Issue 2, pp. 482-489, 01/15/1993 Copyright © 1993 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-T. Labro Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or ""Immuno-Fairy Tales""? Clin. Microbiol. Rev., October 1, 2000; 13(4): 615 - 650. [Abstract] [Full Text] [PDF]

	Copyright © 1993 by American Society of Hematology         Online ISSN: 1528-0020