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@ARTICLE{Langhammer:275962,
      author       = {M. Langhammer and J. Schöpf and T. Jaquet and K. Horn and
                      M. Angel and C. Spohr and D. Christen and F. M. Uhl and T.
                      Maié and H. Jacobi and T. B. Feyerabend$^*$ and J. Huber
                      and M. Panning and C. Sitaru and I. Costa and R. Zeiser$^*$
                      and K. Aumann and H. Becker$^*$ and T. Braunschweig and S.
                      Koschmieder and K. Shoumariyeh$^*$ and M. Huber and M.
                      Schemionek-Reinders and T. Brummer$^*$ and S. Halbach$^*$},
      title        = {{M}ast cell deficiency prevents {BCR}::{ABL}1 induced
                      splenomegaly and cytokine elevation in a {CML} mouse model.},
      journal      = {Leukemia},
      volume       = {37},
      number       = {7},
      issn         = {0887-6924},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2023-00944},
      pages        = {1474-1484},
      year         = {2023},
      note         = {2023 Jul;37(7):1474-1484},
      abstract     = {The persistence of leukemic stem cells (LSCs) represents a
                      problem in the therapy of chronic myeloid leukemia (CML).
                      Hence, it is of utmost importance to explore the underlying
                      mechanisms to develop new therapeutic approaches to cure
                      CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1
                      mouse model for chronic phase CML, we previously
                      demonstrated that the loss of the docking protein GAB2
                      counteracts the infiltration of mast cells (MCs) in the bone
                      marrow (BM) of BCR::ABL1 positive mice. Here, we show for
                      the first time that BCR::ABL1 drives the cytokine
                      independent expansion of BM derived MCs and sensitizes them
                      for FcεRI triggered degranulation. Importantly, we
                      demonstrate that genetic mast cell deficiency conferred by
                      the Cpa3Cre allele prevents BCR::ABL1 induced splenomegaly
                      and impairs the production of pro-inflammatory cytokines.
                      Furthermore, we show in CML patients that splenomegaly is
                      associated with high BM MC counts and that upregulation of
                      pro-inflammatory cytokines in patient serum samples
                      correlates with tryptase levels. Finally, MC-associated
                      transcripts were elevated in human CML BM samples. Thus, our
                      study identifies MCs as essential contributors to disease
                      progression and suggests considering them as an additional
                      target in CML therapy. Mast cells play a key role in the
                      pro-inflammatory tumor microenvironment of the bone marrow.
                      Shown is a cartoon summarizing our results from the mouse
                      model. BCR::ABL1 transformed MCs, as part of the malignant
                      clone, are essential for the elevation of pro-inflammatory
                      cytokines, known to be important in disease initiation and
                      progression.},
      cin          = {D110 / FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)D110-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37161070},
      doi          = {10.1038/s41375-023-01916-x},
      url          = {https://inrepo02.dkfz.de/record/275962},
}