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@PHDTHESIS{Fink:1015901,
author = {Fink, Nicolas Heinrich},
othercontributors = {Huber, Michael and Müller-Newen, Gerhard},
title = {{IL}-2 differentially activates the human mast cell
leukemia cell lines {HMC}-1.1 and {HMC}-1.2},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2025-06630},
pages = {VIII, 65 Seiten : Illustrationen},
year = {2025},
note = {Dissertation, Rheinisch-Westfälische Technische Hochschule
Aachen, 2025},
abstract = {Systemic mastocytosis (SM) is a heterogeneous mast cell
disease that is divided into 3 subtypes. While patients with
an indolent SM mainly suffer from the release of
proinflammatory mediators, the aggressive SM is
characterized by mast cell infiltration into the bone marrow
and organs. The most aggressive variant of SM is mast cell
leukemia (MCL), characterized by the accumulation of mast
cells in the bloodstream. This is associated with a very
short life expectancy of around three months after
diagnosis. The majority (about $90\%)$ of all SM patients
are positive for an activation mutation in the receptor
tyrosine kinase KIT (KITD816V). In addition, the expression
of CD25 on the surface of mast cells is another diagnostic
marker for SM. CD25 constitutes the α subunit of the
heterotrimeric interleukin-2 (IL-2)-receptor, which consists
of one α- , β- and γ-chain. The role of CD25 in mast
cells of SM-patients is not yet sufficiently understood, in
particular a suitable model system is missing. In the
present work, the expression of CD25 and its involvement in
IL-2-dependent signaling pathways in the mast cell leukemia
lines HMC-1.1 and HMC-1.2 were investigated. Using FACS
analysis, CD25 could be detected on the surface of HMC-1.2
cells. The mRNA expression of the α-chain could only be
detected in HMC-1.2 cells using RT-qPCR, while the β- and
γ-chains were expressed in both HMC-1.1 and -1.2 cell
lines. After confirming the expression of the three subunits
of the IL-2 receptor in HMC-1.2 cells, the IL-2-dependent
activation of signaling pathways was analysed using Western
Blot and immunodetection techniques. Here, stimulation of
HMC-1.2 cells with IL-2 increased the phosphorylation of the
transcription factor STAT5, which is dependent on Janus
kinase (JAK) activation. An IL-2-mediated expression of the
STAT5 target genes CISH and OSM could also be detected. The
IL-2-mediated STAT5 phosphorylation and the activation of
STAT5 target genes could be suppressed using the JAK
inhibitor Ruxolitinib. The results of this work show that
HMC-1.2 cells express the diagnostic CD25-marker and that
the activation of IL-2-dependent signaling pathways is
functional in these cells. It could be shown for the first
time that HMC-1.2 cells are a suitable model system for the
analysis of CD25- dependent mechanisms. This will help to
advance the understanding of the role of the diagnostic
marker CD25 in mast cell leukemia.},
cin = {513000-3 ; 924720},
ddc = {610},
cid = {$I:(DE-82)513000-3_20140620$},
typ = {PUB:(DE-HGF)11},
url = {https://publications.rwth-aachen.de/record/1015901},
}
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