Defining the Extracellular Matrix Composition of the Acute Myeloid Leukemia Cell Niche: Towards Development of a Functional 3D Drug Screening System

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dc.contributor.advisorSachlos, Eleftherios
dc.contributor.authorSadetckaia, Vladislava
dc.date.accessioned2022-08-08T15:54:24Z
dc.date.available2022-08-08T15:54:24Z
dc.date.copyright2022-04-21
dc.date.issued2022-08-08
dc.date.updated2022-08-08T15:54:24Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractAcute Myeloid Leukemia is a heterogeneous hematopoietic malignancy, which has been shown to modify the bone marrow microenvironment towards cooperating with the cancer cell to promote their proliferation. In this research I optimized a procedure for growing AML cells in a novel culture system in vitro in order to provide the cells with a microenvironment more closely resembling the native cell niche. Next, an analysis of various ECM components was undertaken to assess whether their presence may affect AML cell survival. In a proof-of-concept study, I employed the novel culture system to analyze the effect of 160 chemical agents on cell survival and compared the traditional polystyrene cultures with the novel 2D and 3D collagen culture systems. By recapitulating the tumor microenvironment with three-dimensional collagen scaffolds, I was able to demonstrate a microenvironment-dependent variation in drug response and identify novel targets that may not have been detected with a traditional screening assay.
dc.identifier.urihttp://hdl.handle.net/10315/39641
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectMolecular biology
dc.subject.keywordsCancer
dc.subject.keywordsLeukemia
dc.subject.keywordsCollagen scaffolds
dc.subject.keywordsBiomaterials
dc.subject.keywordsDrug screening
dc.subject.keywordsHigh-throughput
dc.subject.keywordsAML
dc.subject.keywordsHSC
dc.subject.keywordsHematopoiesis
dc.subject.keywordsECM
dc.subject.keywordsExtracellular matrix
dc.subject.keywordsNiche
dc.subject.keywordsBone marrow
dc.subject.keywordsElastin
dc.subject.keywordsHydroxyapatite
dc.subject.keywordsSynthetic scaffolds
dc.subject.keywords3D cultures
dc.titleDefining the Extracellular Matrix Composition of the Acute Myeloid Leukemia Cell Niche: Towards Development of a Functional 3D Drug Screening System
dc.typeElectronic Thesis or Dissertation

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