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@ARTICLE{Ludwig:274136,
      author       = {M. Ludwig and A. Basti and M. Yalçin and J. Schulte$^*$
                      and A. Relógio},
      title        = {{M}olecular characterization of the circadian clock in
                      paediatric leukaemia patients: a prospective study
                      protocol.},
      journal      = {BMC pediatrics},
      volume       = {23},
      number       = {1},
      issn         = {1471-2431},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-00446},
      pages        = {105},
      year         = {2023},
      abstract     = {In many organisms, including humans, the timing of cellular
                      processes is regulated by the circadian clock. At the
                      molecular level the core-clock consists of
                      transcriptional-translational-feedback loops including
                      several genes such as BMAL1, CLOCK, PERs and CRYs generating
                      circa 24-h rhythms in the expression of about $40\%$ of our
                      genes across all tissues. Previously these core-clock genes
                      have been shown to be differentially expressed in various
                      cancers. Albeit a significant effect in treatment
                      optimization of chemotherapy timing in paediatric acute
                      lymphoblastic leukaemia has previously been reported, the
                      mechanistic role played by the molecular circadian clock in
                      acute paediatric leukaemia remains elusive.To characterize
                      the circadian clock, we will recruit patients with newly
                      diagnosed leukaemia and collect time course saliva and blood
                      samples, as well as a single bone marrow sample. From the
                      blood and bone marrow samples nucleated cells will be
                      isolated and further undergo separation into CD19+ and CD19-
                      cells. qPCR is performed on all samples targeting the
                      core-clock genes including BMAL1, CLOCK, PER2 and CRY1.
                      Resulting data will be analysed for circadian rhythmicity
                      using the RAIN algorithm and harmonic regression.To the best
                      of our knowledge this is the first study aiming to
                      characterize the circadian clock in a cohort of paediatric
                      patients with acute leukaemia. In the future we hope to
                      contribute to uncovering further vulnerabilities of cancers
                      associated with the molecular circadian clock and in
                      particular adjust chemotherapy accordingly, leading to more
                      targeted toxicity, and hence decreased systemic toxicities.},
      keywords     = {ALL (Other) / AML (Other) / Circadian profiling (Other) /
                      Circadian rhythms (Other) / Clock genes (Other) / Paediatric
                      leukaemia (Other) / Rhythmicity analysis (Other)},
      cin          = {BE01},
      ddc          = {610},
      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:36870963},
      doi          = {10.1186/s12887-023-03921-6},
      url          = {https://inrepo02.dkfz.de/record/274136},
}