Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/358442
Full metadata record
DC FieldValueLanguage
dc.coverage.spatial
dc.date.accessioned2022-01-27T12:43:55Z-
dc.date.available2022-01-27T12:43:55Z-
dc.identifier.urihttp://hdl.handle.net/10603/358442-
dc.description.abstractBone marrow micro-environment is a reservoir and sanctuary for the maintenance, survival and the behavior of the hematopoietic stem cells. Malignant myeloblasts rearchitects the bone marrow micro-environment for a deleterious symbiotic relationship via contact dependent and independent manner. Henceforth, we undertook an unbiased approach to understand the interactions between the major components of the bone marrow micro-environment mesenchymal stromal cells and the leukemic cells. Our gene expression profiling results strongly corroborated with the existing literature of bone marrow micro-environment mediated drug resistance. Prominent signaling pathways which were up regulated was NF-kB and PI3KAKT genes which prompted us to evaluate these signaling pathways in the protective effect provided by the stromal cells to leukemic cells against daunorubicin and cytosine arabinoside. We employed, small molecules and drug screening approach targeting these pathways with specific inhibitors significantly overcome the bone marrow microenvironment mediated drug resistance both in a contact dependent and independent system. To further evaluate the paracrine mediated protective effect offered by the stromal cells we focused on the mechanisms of cell-cell contact and observed the importance of the extracellular vesicles (EVs) in both the physiological and pathological conditions. EVs carry signaling molecules such as miRNA, proteins, and subcellular organelles and regulates the signaling cascades in the receiving cells. Inhibiting the extracellular vesicles secretion abrogated protective effect offered by the stromal cells both in a contact dependent and independent manner and down regulated the NF-kB and PI3K-AKT signaling. The study highlights the complexity of the bone marrow micro-environment in the promoting drug resistance and identified multiple players and targets to overcome the protective effect using pharmacological and genetic knockdown and over expression approaches. newline
dc.format.extent252
dc.languageEnglish
dc.relation
dc.rightsuniversity
dc.titleEvaluation of Environment Mediated Innate Drug Resistance in Leukemia
dc.title.alternative
dc.creator.researcherHamenth Kumar P
dc.subject.keywordAcute Myeloid Leukemia
dc.subject.keywordEnvironment Mediated Drug Resistance
dc.subject.keywordExtracellular Vesicles
dc.subject.keywordLeukemia
dc.description.note
dc.contributor.guideVikram Mathews and Eunice Sindhuvi E
dc.publisher.placeChennai
dc.publisher.universityThe Tamil Nadu Dr. M.G.R. Medical University
dc.publisher.institutionDepartment of Medical
dc.date.registered
dc.date.completed2019
dc.date.awarded
dc.format.dimensions
dc.format.accompanyingmaterialNone
dc.source.universityUniversity
dc.type.degreePh.D.
Appears in Departments:Department of Medical

Files in This Item:
File Description SizeFormat 
01_title.pdfAttached File185.56 kBAdobe PDFView/Open
02_certificate.pdf1.04 MBAdobe PDFView/Open
03_preliminary pages.pdf401.77 kBAdobe PDFView/Open
04_chapter 1.pdf440.85 kBAdobe PDFView/Open
05_chapter 2.pdf182.73 kBAdobe PDFView/Open
06_chapter 3.pdf3.88 MBAdobe PDFView/Open
07_chapter 4.pdf437.31 kBAdobe PDFView/Open
08_chapter 5.pdf1.28 MBAdobe PDFView/Open
09_chapter 6.pdf10.79 MBAdobe PDFView/Open
10_chapter 7.pdf372.49 kBAdobe PDFView/Open
11_bibliography.pdf350.26 kBAdobe PDFView/Open
12_publications ans abstract.pdf522.14 kBAdobe PDFView/Open
13_plagiarism report.pdf216.14 kBAdobe PDFView/Open
14_annexures.pdf9.34 MBAdobe PDFView/Open
80_recommendation.pdf523.62 kBAdobe PDFView/Open


Items in Shodhganga are licensed under Creative Commons Licence Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).

Altmetric Badge: