• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Effect of inhibiting Pim-1 kinase in acute myeloid leukemia with FLT3 internal tandem duplication

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    shivanikapoor_umaryland_0373N_ ...
    Size:
    3.338Mb
    Format:
    PDF
    Download
    Author
    Kapoor, Shivani
    Advisor
    Baer, Maria R.
    Date
    2016
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    The project is focused on combinatorial treatment involving downstream inhibitors of FLT3 signaling, representing a promising approach for treating AML patients with FLT3-ITD. Pim-1 kinase is upregulated downstream of FLT3-ITD pathway by a positive feedback loop. The goal of this work was to characterize Pim kinase inhibitor (PIM447, currently in clinical trials) sensitization of cells FLT3-ITD to apoptosis induction by combination of FLT3 inhibitors and chemotherapy drugs. PIM447 sensitizes FLT3-ITD cells to FLT3 inhibitors and topoisomerase-2 inhibitors. Co-treatment with the Pim kinase inhibitor AZD1208 and FLT3 inhibitor quizartinib was found to enhance apoptosis of cells FLT3-ITD post-translationally, decreasing expression of the anti-apoptotic protein Mcl-1 through increased proteasomal degradation and in association with decreased expression of deubiquitinase USP9X. PIM447 in combination with FLT3 inhibitors as quizartinib, sorafenib and midostaurin and topoisomerase-2 inhibitors as daunorubicin, mitoxantrone and etoposide in FLT3-ITD cells, induced a dose response dependent increasing apoptosis.
    Description
    University of Maryland, Baltimore. Medical and Research Technology. M.S. 2016
    Keyword
    Drug Therapy, Combination
    Leukemia, Myeloid, Acute--drug therapy
    Proto-Oncogene Proteins c-pim-1--antagonists & inhibitors
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/6279
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.