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@ARTICLE{He:179057,
      author       = {L. He and C. Arnold and J. Thoma and C. Rohde and M.
                      Kholmatov and S. Garg and C.-C. Hsiao and L. Viol$^*$ and K.
                      Zhang$^*$ and R. Sun$^*$ and C. Schmidt and M. Janssen and
                      T. MacRae and K. Huber and C. Thiede and J. Hébert and G.
                      Sauvageau and J. Spratte and H. Fluhr and G. Aust and C.
                      Müller-Tidow and C. Niehrs$^*$ and G. Pereira$^*$ and J.
                      Hamann and M. Tanaka and J. B. Zaugg and C. Pabst},
      title        = {{CDK}7/12/13 inhibition targets an oscillating leukemia
                      stem cell network and synergizes with venetoclax in acute
                      myeloid leukemia.},
      journal      = {EMBO molecular medicine},
      volume       = {14},
      number       = {4},
      issn         = {1715-4684},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {DKFZ-2022-00435},
      pages        = {e14990},
      year         = {2022},
      note         = {DKFZ-ZMBH Alliance / 2022 Apr 7;14(4):e14990},
      abstract     = {The heterogeneous response of acute myeloid leukemia (AML)
                      to current anti-leukemic therapies is only partially
                      explained by mutational heterogeneity. We previously
                      identified GPR56 as a surface marker associated with poor
                      outcome across genetic groups, which characterizes two
                      leukemia stem cell (LSC)-enriched compartments with
                      different self-renewal capacities. How these compartments
                      self-renew remained unclear. Here, we show that GPR56+ LSC
                      compartments are promoted in a complex network involving
                      epithelial-to-mesenchymal transition (EMT) regulators
                      besides Rho, Wnt, and Hedgehog (Hh) signaling. Unexpectedly,
                      Wnt pathway inhibition increased the more immature, slowly
                      cycling GPR56+ CD34+ fraction and Hh/EMT gene expression,
                      while Wnt activation caused opposite effects. Our data
                      suggest that the crucial role of GPR56 lies in its ability
                      to co-activate these opposing signals, thus ensuring the
                      constant supply of both LSC subsets. We show that CDK7
                      inhibitors suppress both LSC-enriched subsets in vivo and
                      synergize with the Bcl-2 inhibitor venetoclax. Our data
                      establish reciprocal transition between LSC compartments as
                      a novel concept underlying the poor outcome in GPR56high AML
                      and propose combined CDK7 and Bcl-2 inhibition as
                      LSC-directed therapy in this disease.},
      keywords     = {AML (Other) / CDK7 inhibition (Other) / GPR56 (Other) /
                      leukemia stem cell (Other) / self-renewal (Other)},
      cin          = {A180 / A050},
      ddc          = {610},
      cid          = {I:(DE-He78)A180-20160331 / I:(DE-He78)A050-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35253392},
      doi          = {10.15252/emmm.202114990},
      url          = {https://inrepo02.dkfz.de/record/179057},
}