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@ARTICLE{Sartorius:301917,
      author       = {S. Sartorius and L. Bramè$^*$ and J. Proba and A. Gauert
                      and N. Olk and J. Lazaro and A. Eggert and C. Eckert and A.
                      H. Hagemann$^*$},
      title        = {{R}apid in vivo {D}rug {R}esponse {P}rediction {U}sing
                      {L}eukemia {C}ell {G}rafts in {Z}ebrafish {E}mbryos.},
      journal      = {JoVE journal},
      volume       = {23},
      number       = {219},
      issn         = {1940-087X},
      address      = {Cambridge, MA},
      publisher    = {JoVE},
      reportid     = {DKFZ-2025-01187},
      pages        = {67451},
      year         = {2025},
      note         = {ISSN 1940-087X},
      abstract     = {Zebrafish xenotransplantation is a pivotal technique for
                      investigating human cancer pathogenesis and predicting
                      individual drug responses. This document introduces a
                      streamlined protocol (ZefiX) for expanding primary B-cell
                      precursor acute lymphoblastic leukemia (BCP-ALL) patient
                      samples or immortalized cell lines in transiently
                      immunosuppressed zebrafish embryos, utilizing flow cytometry
                      for high-resolution single-cell analysis of treatment
                      responses. Compared to solid tumor engraftments, leukemia
                      cells profit significantly from a morpholino antisense
                      oligonucleotide-based suppression of macrophage and
                      neutrophil differentiating factors during the assay. Flow
                      cytometry analysis of dissociated graft cells enables
                      precise evaluation of cell count, proliferation rate, and
                      vitality after treatment on a per-cell basis. This approach
                      has been validated using targeted therapeutics such as
                      venetoclax and dasatinib, with treatment outcomes compared
                      to clinical records of related patient samples and
                      traditional 2D culture controls. Notably, the protocol is
                      completed within 7 days, aligning with clinical
                      decision-making timelines. The methodology is adaptable for
                      testing selected drugs in various cancer types, including
                      solid tumors, thereby supporting personalized therapeutic
                      strategies. However, limitations on the number of drugs that
                      can be assessed, likely due to pharmacokinetic constraints
                      in zebrafish embryos, should be considered.},
      keywords     = {Zebrafish: embryology / Animals / Humans / Antineoplastic
                      Agents: pharmacology / Flow Cytometry: methods / Precursor
                      B-Cell Lymphoblastic Leukemia-Lymphoma: drug therapy /
                      Precursor B-Cell Lymphoblastic Leukemia-Lymphoma: pathology
                      / Antineoplastic Agents (NLM Chemicals)},
      cin          = {BE01},
      ddc          = {570},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40489456},
      doi          = {10.3791/67451},
      url          = {https://inrepo02.dkfz.de/record/301917},
}