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@ARTICLE{RichterPechaska:179973,
      author       = {P. Richter-Pechańska and J. B. Kunz and T. Rausch and B.
                      Erarslan-Uysal and B. Bornhauser and V. Frismantas and Y.
                      Assenov$^*$ and M. Zimmermann and M. Happich and C. von
                      Knebel-Doeberitz and N. von Neuhoff and R. Köhler and M.
                      Stanulla and M. Schrappe and G. Cario and G. Escherich and
                      R. Kirschner-Schwabe$^*$ and C. Eckert$^*$ and S. Avigad and
                      S. M. Pfister$^*$ and M. U. Muckenthaler and J.-P. Bourquin
                      and J. O. Korbel and A. Kulozik$^*$},
      title        = {{P}ediatric {T}-{ALL} type-1 and type-2 relapses develop
                      along distinct pathways of clonal evolution.},
      journal      = {Leukemia},
      volume       = {36},
      number       = {7},
      issn         = {0887-6924},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2022-01013},
      pages        = {1759-1768},
      year         = {2022},
      note         = {#LA:B062# / 2022 Jul;36(7):1759-1768},
      abstract     = {The mechanisms underlying T-ALL relapse remain essentially
                      unknown. Multilevel-omics in 38 matched pairs of initial and
                      relapsed T-ALL revealed 18 $(47\%)$ type-1 (defined by being
                      derived from the major ancestral clone) and 20 $(53\%)$
                      type-2 relapses (derived from a minor ancestral clone). In
                      both types of relapse, we observed known and novel drivers
                      of multidrug resistance including MDR1 and MVP, NT5C2 and
                      JAK-STAT activators. Patients with type-1 relapses were
                      specifically characterized by IL7R upregulation. In
                      remarkable contrast, type-2 relapses demonstrated (1)
                      enrichment of constitutional cancer predisposition gene
                      mutations, (2) divergent genetic and epigenetic remodeling,
                      and (3) enrichment of somatic hypermutator phenotypes,
                      related to BLM, BUB1B/PMS2 and TP53 mutations. T-ALLs that
                      later progressed to type-2 relapses exhibited a complex
                      subclonal architecture, unexpectedly, already at the time of
                      initial diagnosis. Deconvolution analysis of ATAC-Seq
                      profiles showed that T-ALLs later developing into type-1
                      relapses resembled a predominant immature thymic T-cell
                      population, whereas T-ALLs developing into type-2 relapses
                      resembled a mixture of normal T-cell precursors. In sum, our
                      analyses revealed fundamentally different mechanisms driving
                      either type-1 or type-2 T-ALL relapse and indicate that
                      differential capacities of disease evolution are already
                      inherent to the molecular setup of the initial leukemia.},
      cin          = {B062 / HD01 / BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)BE01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35585141},
      doi          = {10.1038/s41375-022-01587-0},
      url          = {https://inrepo02.dkfz.de/record/179973},
}