Characterization of the Leukemia Initiating Cell in Human Acute Myeloid Leukemia
Ihme, Erika Ruth Susann
The aim of this thesis was to establish a miRNA profile of functionally validated LICs from patients suffering from AML. To achieve this, multicolor staining protocols were established to highly purify sorted LIC and non-LIC populations from patients with AML as well for sorting their normal counterparts from bone marrow of healthy donors. In a second step, functional validation of the LIC properties was achieved by performing successfully transplantations into the immunocompromised xenograft NSG mouse model. In this study 22 de novo AML samples were included and sorted for their leukemic stem- and progenitor subpopulations as well as the more differentiated leukemic CD34- fraction. In total 11 patient samples were able to form a human leukemia graft in NSG mice with a tendency of higher engraftment in FLT3 mutated and aberrant karyotype patients. By performing next generation sequencing analysis, a miRNA signature of these validated LICs was established performing comparative analysis between the LIC and the leukemic non-LIC fraction or the normal human bone marrow counterparts. Therefore, this study is the first one that has established a miRNA expression pattern in in vivo validated AML LICs.
Subject HeadingsAcute myeloid leukemia [MeSH]