• Login
    View Item 
    •   Home
    • Academic Divisions
    • Biological and Environmental Science & Engineering (BESE)
    • Biological and Environmental Science and Engineering (BESE) Division
    • View Item
    •   Home
    • Academic Divisions
    • Biological and Environmental Science & Engineering (BESE)
    • Biological and Environmental Science and Engineering (BESE) Division
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguideTheses and Dissertations LibguideSubmit an Item

    Statistics

    Display statistics

    Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Mansour Aldehaiman Ms Thesis_Final.pdf
    Size:
    1.678Mb
    Format:
    PDF
    Description:
    Mansour Aldehaiman Ms Thesis_Final
    Download
    Type
    Thesis
    Authors
    Aldehaiman, Mansour M. cc
    Advisors
    Merzaban, Jasmeen cc
    Committee members
    Mahfouz, Magdy M. cc
    Arold, Stefan T. cc
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Science and Engineering (BESE) Division
    Date
    2018-04
    Embargo End Date
    2019-05-23
    Permanent link to this record
    http://hdl.handle.net/10754/627947
    
    Metadata
    Show full item record
    Access Restrictions
    At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis became available to the public after the expiration of the embargo on 2019-05-23.
    Abstract
    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target for AML once its levels are altered.
    Citation
    Aldehaiman, M. M. (2018). Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells. KAUST Research Repository. https://doi.org/10.25781/KAUST-1QR9T
    DOI
    10.25781/KAUST-1QR9T
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-1QR9T
    Scopus Count
    Collections
    Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; MS Theses

    entitlement

     
    DSpace software copyright © 2002-2023  DuraSpace
    Quick Guide | Contact Us | KAUST University Library
    Open Repository is a service hosted 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. For anonymous users the allowed maximum amount is 50 search results.

    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.