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@ARTICLE{Kempter:299835,
      author       = {T. Kempter and P. Richter-Pechańska and K. Michel and T.
                      Rausch and B. Erarslan-Uysal and C. Eckert and M. Zimmermann
                      and M. Stanulla and M. Schrappe and G. Cario and S. Köhrer
                      and A. Attarbaschi and J. O. Korbel and J. B. Kunz and A.
                      Kulozik$^*$},
      title        = {{S}ubclonal {TP}53 and {KRAS} variants combined with poor
                      treatment response identify ultrahigh-risk pediatric
                      patients with {T}-{ALL}.},
      journal      = {Blood advances},
      volume       = {9},
      number       = {6},
      issn         = {2473-9529},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-00572},
      pages        = {1267 - 1279},
      year         = {2025},
      note         = {#LA:A400#},
      abstract     = {Variations in the TP53 and KRAS genes indicate a
                      particularly adverse prognosis in relapsed pediatric T-cell
                      acute lymphoblastic leukemia (T-ALL). We hypothesized that
                      these variations might be subclonally present at disease
                      onset and contribute to relapse risk. To test this, we
                      examined 2 cohorts of children diagnosed with T-ALL: cohort
                      1 with 81 patients who relapsed and 79 who matched
                      nonrelapsing controls, and cohort 2 with 226 consecutive
                      patients, 30 of whom relapsed. In cohort 1, targeted
                      sequencing revealed TP53 clonal and subclonal variants in 6
                      of 81 relapsing patients but none in the nonrelapsing group
                      (P = .014). KRAS alterations were found in 9 of 81 relapsing
                      patients compared with 2 of 79 nonrelapsing patients (P =
                      .032). Survival analysis showed that none of the relapsed
                      patients with TP53 and/or KRAS alterations survived, whereas
                      19 of 67 relapsed patients without such variants did, with a
                      minimum follow-up time of 3 years (P = .023). In cohort 2,
                      none of the relapsing patients but 10 of 196 nonrelapsing
                      patients carried TP53 or KRAS variants, indicating that
                      mutation status alone does not predict poor prognosis. All
                      10 nonrelapsing patients with mutations had a favorable
                      early treatment response. Among the total cohort of 386
                      patients, 188 showed poor treatment response, of whom 69
                      relapsed. Of these poor responders, 9 harbored TP53 or KRAS
                      variants. In conclusion, subclonal TP53 and KRAS alterations
                      identified at the time of initial diagnosis, along with a
                      poor treatment response, characterize a subset of children
                      with T-ALL who face a dismal prognosis and who may benefit
                      from alternative treatment approaches.},
      keywords     = {Humans / Tumor Suppressor Protein p53: genetics /
                      Proto-Oncogene Proteins p21(ras): genetics / Child /
                      Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: genetics /
                      Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: mortality
                      / Precursor T-Cell Lymphoblastic Leukemia-Lymphoma:
                      diagnosis / Precursor T-Cell Lymphoblastic
                      Leukemia-Lymphoma: therapy / Male / Female / Child,
                      Preschool / Prognosis / Adolescent / Infant / Mutation /
                      Treatment Outcome / Tumor Suppressor Protein p53 (NLM
                      Chemicals) / Proto-Oncogene Proteins p21(ras) (NLM
                      Chemicals) / KRAS protein, human (NLM Chemicals) / TP53
                      protein, human (NLM Chemicals)},
      cin          = {A400},
      ddc          = {610},
      cid          = {I:(DE-He78)A400-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39808796},
      doi          = {10.1182/bloodadvances.2024014209},
      url          = {https://inrepo02.dkfz.de/record/299835},
}