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@ARTICLE{SchulzeEdinghausen:144006,
      author       = {L. Schulze-Edinghausen$^*$ and C. Dürr$^*$ and S.
                      Öztürk$^*$ and M. Zucknick and A. Benner$^*$ and V.
                      Kalter$^*$ and S. Ohl$^*$ and V. Close$^*$ and P. Wuchter
                      and S. Stilgenbauer and P. Lichter$^*$ and M. Seiffert$^*$},
      title        = {{D}issecting the {P}rognostic {S}ignificance and
                      {F}unctional {R}ole of {P}rogranulin in {C}hronic
                      {L}ymphocytic {L}eukemia.},
      journal      = {Cancers},
      volume       = {11},
      number       = {6},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2019-01557},
      pages        = {822},
      year         = {2019},
      abstract     = {Chronic lymphocytic leukemia (CLL) is known for its strong
                      dependency on the tumor microenvironment. We found
                      progranulin (GRN), a protein that has been linked to
                      inflammation and cancer, to be upregulated in the serum of
                      CLL patients compared to healthy controls, and increased GRN
                      levels to be associated with an increased hazard for disease
                      progression and death. This raised the question of whether
                      GRN is a functional driver of CLL. We observed that
                      recombinant GRN did not directly affect viability,
                      activation, or proliferation of primary CLL cells in vitro.
                      However, GRN secretion was induced in co-cultures of CLL
                      cells with stromal cells that enhanced CLL cell survival.
                      Gene expression profiling and protein analyses revealed that
                      primary mesenchymal stromal cells (MSCs) in co-culture with
                      CLL cells acquire a cancer-associated fibroblast-like
                      phenotype. Despite its upregulation in the co-cultures, GRN
                      treatment of MSCs did not mimic this effect. To test the
                      relevance of GRN for CLL in vivo, we made use of the
                      Eμ-TCL1 CLL mouse model. As we detected strong GRN
                      expression in myeloid cells, we performed adoptive transfer
                      of Eμ-TCL1 leukemia cells to bone marrow chimeric Grn-/-
                      mice that lack GRN in hematopoietic cells. Thereby, we
                      observed that CLL-like disease developed comparable in
                      Grn-/- chimeras and respective control mice. In conclusion,
                      serum GRN is found to be strongly upregulated in CLL, which
                      indicates potential use as a prognostic marker, but there is
                      no evidence that elevated GRN functionally drives the
                      disease.},
      cin          = {B060 / C060 / B061 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B061-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31200555},
      doi          = {10.3390/cancers11060822},
      url          = {https://inrepo02.dkfz.de/record/144006},
}