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dc.contributor.advisorCaldwell, Charles W., M.D.eng
dc.contributor.advisorBennett, Lyndaeng
dc.contributor.authorKaiwar, Charueng
dc.date.issued2011eng
dc.date.submitted2011 Springeng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on August 23, 2012).eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionThesis advisors: Charles W. Caldwell M.D., PhD and Lynda B. Bennett PhDeng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionM.S. University of Missouri-Columbia 2011.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- pathology.eng
dc.description"May 2011"eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] B-cell Chronic Lymphocytic Leukemia (B-CLL) is the most common hematological malignancy in United States[1], characterized by CD5+ B-lymphocytes in peripheral blood. Deregulation of the Notch signaling pathway has been suggested to contribute to B-CLL pathogenesis [2-4]. Our objective was to characterize the differential expression of the Notch pathway genes in B-CLL cell lines as compared to normal B-cells and to determine if inhibiting the Notch pathway using γsecretase inhibitors (GSIs would lead to increased death in B-CLL cells. We observed over-expression of Notch pathway genes in three B-CLL cell lines. Treatment with either of the GSIs, DAPT(N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester) or Compound E, failed to have any effect on proliferation or death of these cells. Moreover,there was no alteration in transcription of downstream Notch target genes Hairy and enhancer of split 1, (HES1) Hairy/enhancer-of-split related with YRPW motif 1( HEY1), or Deltex homolog 1 (DTX1) in treated vs. untreated cells. These findings suggest that although Notch pathway genes seem to up regulated in B-B-CLL,inhibition of the pathway does not lead to cell death nor does it alter Notch target gene transcripton. One explanation could be that the Notch receptor is constitutively active in B-CLL as in other hematological malignancies like Tcell-Acute Lymphoblastic Leukemia (T-ALL)[5]. Alternatively, the survival of leukemic cells in B-CLL as well as transcription of the target genes examined, may be a combined result of signaling via the Notch and other signaling pathways such as Jak-STAT, Wnt and Sonic hedgehog, which have roles in B-CLL pathogenesis[6-10].eng
dc.format.extentv, 22 pageseng
dc.identifier.urihttp://hdl.handle.net/10355/14912
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri-Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess to files is limited to the University of Missouri--Columbia.eng
dc.subjectnotch signalingeng
dc.subjectleukemiaeng
dc.subjectcell deatheng
dc.subjectgene transcriptoneng
dc.titleDeregulation of the notch signaling pathway N B-cell chronic lymphocytic leukemiaeng
dc.typeThesiseng
thesis.degree.disciplinePathology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelMasterseng
thesis.degree.nameM.S.eng


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