[{"key":"dc.contributor.author","value":"Guan, Yinghui","language":null},{"key":"dc.date.accessioned","value":"2009-11-11T05:59:31Z","language":null},{"key":"dc.date.available","value":"2009-11-11T05:59:31Z","language":null},{"key":"dc.date.issued","value":"2002","language":null},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/14765","language":null},{"key":"dc.description.abstract","value":"We have detected a high concentration of cytogenetically normal long term culture-initiating\r\ncells (LTC-IC) in the peripheral blood (PB) of 12 patients with newly-diagnosed AML. To\r\ndetermine if these progenitors originated from normal polyclonal hematopoiesis the PCR-based\r\nhuman androgen receptor allele (HUMARA) assay was used to study PB cells from 5 female\r\npatients with cytogenetically abnormal AML. In 4\/5 samples cytogenetics and clonality data\r\nfrom LTC indicate that a substantial number of normal polyclonal hematopoietic progenitors\r\noften persist in AML PB at diagnosis. However, the fifth AML sample contrasted with the others\r\nsince the HUMARA assay demonstrated that LTC-derived colonies were predominantly clonal\r\nalthough the majority of the progenitors were cytogenetically normal. Thus, it appears that the\r\nabnormality detected on routine cytogenetics is not a reliable marker of the leukemic clone in\r\nthis case.\r\n\r\nThe second goal of this thesis was to characterize cycling status of different leukemic\r\nprogenitors. An overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the\r\nproliferative status of malignant progenitors detected in CFC, LTC-IC and NOD\/SCID mouse\r\nleukemia initiating cell (NOD\/SL-IC) assays from the peripheral blood of 15 patients with\r\nnewly-diagnosed AML. FISH analysis of colonies from CFC and LTC-IC assays confirmed that\r\nmost cytogenetically abnormal CFC and LTC-IC from the 15 samples as well as cytogenetically\r\nnormal LTC-IC detected were actively cycling. However, the same assay has demonstrated that\r\nsome AML LTC-IC and most NOD\/SL-IC were largely quiescent.\r\nThe growth factor responsiveness of quiescent AML cells was then studied and their\r\nfunctional properties compared to those of AML cells in active cell cycle. Hoechst\r\n33342\/Pyronin Y staining and FACS sorting were used to isolate Go cells in from the G1 and\r\nS\/G2+M subpopulations of peripheral blood cells from 4 newly diagnosed AML patients. Go AML cells from these patients exhibited a strong tendency to enter active cell cycle when\r\ncultured even in the absence of supportive growth factors. LTC-ICs were easily detected among\r\ncycling AML cells that had been cultured for 72 hours. In contrast, the exit from Go dramatically\r\nreduced the ability of AML progenitors to engraft in mouse bone marrow.","language":"en"},{"key":"dc.format.extent","value":"7520766 bytes","language":null},{"key":"dc.format.mimetype","value":"application\/pdf","language":null},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":null},{"key":"dc.rights","value":"For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https:\/\/open.library.ubc.ca\/terms_of_use.","language":null},{"key":"dc.title","value":"Clonality and cycling status of leukemic progenitors from patients with acute myeloid leukemia (AML)","language":"en"},{"key":"dc.type","value":"Text","language":null},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Pathology","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":null},{"key":"dc.date.graduation","value":"2002-11","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":null},{"key":"dc.description.affiliation","value":"Pathology and Laboratory Medicine, Department of","language":null},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]