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@ARTICLE{Stelmach:241122,
      author       = {P. Stelmach$^*$ and A. Trumpp$^*$},
      title        = {{L}eukemic stem cells and therapy resistance in acute
                      myeloid leukemia.},
      journal      = {Haematologica},
      volume       = {108},
      number       = {2},
      issn         = {0390-6078},
      address      = {Pavia},
      publisher    = {Ferrata Storti Foundation},
      reportid     = {DKFZ-2023-00242},
      pages        = {353 - 366},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance / #EA:A010#LA:A010#},
      abstract     = {A major obstacle in the treatment of acute myeloid leukemia
                      (AML) is refractory disease or relapse after achieving
                      remission. The latter arises from a few therapy-resistant
                      cells within minimal residual disease (MRD). Resistant cells
                      with long-term self-renewal capacity that drive clonal
                      outgrowth are referred to as leukemic stem cells (LSC). The
                      cancer stem cell concept considers LSC as relapse-initiating
                      cells residing at the top of each genetically defined AML
                      subclone forming epigenetically controlled downstream
                      hierarchies. LSC display significant phenotypic and
                      epigenetic plasticity, particularly in response to therapy
                      stress, which results in various mechanisms mediating
                      treatment resistance. Given the inherent chemotherapy
                      resistance of LSC, targeted strategies must be incorporated
                      into first-line regimens to prevent LSC-mediated AML
                      relapse. The combination of venetoclax and azacitidine is a
                      promising current strategy for the treatment of AML LSC.
                      Nevertheless, the selection of patients who would benefit
                      either from standard chemotherapy or venetoclax +
                      azacitidine treatment in first-line therapy has yet to be
                      established and the mechanisms of resistance still need to
                      be discovered and overcome. Clinical trials are currently
                      underway that investigate LSC susceptibility to first-line
                      therapies. The era of single-cell multi-omics has begun to
                      uncover the complex clonal and cellular architectures and
                      associated biological networks. This should lead to a better
                      understanding of the highly heterogeneous AML at the inter-
                      and intra-patient level and identify resistance mechanisms
                      by longitudinal analysis of patients' samples. This review
                      discusses LSC biology and associated resistance mechanisms,
                      potential therapeutic LSC vulnerabilities and current
                      clinical trial activities.},
      subtyp        = {Review Article},
      cin          = {A010 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36722405},
      doi          = {10.3324/haematol.2022.280800},
      url          = {https://inrepo02.dkfz.de/record/241122},
}