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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},
}