Characterization of the Leukemia Initiating Cell in Human Acute Myeloid Leukemia
Dissertation
Authors
Ihme, Erika Ruth Susann
Faculties
Medizinische FakultätAbstract
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.
Date created
2014
Subject Headings
Acute myeloid leukemia [MeSH]Leukemia [MeSH]
Keywords
fluorescence activated cell sorter (FACS); granulocyte-macrophage progenitor (GMP); hematopoietic stem cell; leukemia initiating cell (LIC); lymphoid-primed multipotent progenitor (LMPP); miRNA; stem cell; xenotransplantationDewey Decimal Group
DDC 610 / Medicine & healthMetadata
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Ihme, Erika Ruth Susann (2016): Characterization of the Leukemia Initiating Cell in Human Acute Myeloid Leukemia. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-4241