• Medientyp: E-Artikel
  • Titel: Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
  • Beteiligte: Braun, Till [Verfasser:in]; Dechow, Annika [Verfasser:in]; Friedrich, Gregor [Verfasser:in]; Seifert, Michael [Verfasser:in]; Stachelscheid, Johanna [Verfasser:in]; Herling, Marco [Verfasser:in]
  • Erschienen: Lausanne: Frontiers Research Foundation, [2023]
  • Erschienen in: Frontiers in oncology ; 11, (2021)
  • Sprache: Englisch
  • Schlagwörter: TCL1A ; T-PLL ; clonal evolution ; ATM ; pathogenesis
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  • Beschreibung: T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is atypically aggressively growing and chemotherapy-resistant malignancy with a poorprognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memorytypeeffector functions. Constitutive transcriptional activation of genes of the T-cellleukemia 1 (TCL1) family based on genomic inversions/translocations is recognized asa key event in T-PLL’s pathogenesis. TCL1’s multiple effector pathways include theenhancement of T-cell receptor (TCR) signals. New molecular dependencies aroundresponses to DNA damage, including repair and apoptosis regulation, as well asalterations of cytokine and non-TCR activation signaling were identified as perturbedhallmark pathways within the past years. We currently witness these vulnerabilities to beinterrogated in first pre-clinical concepts and initial clinical testing in relapsed/refractory TPLLpatients. We summarize here the current knowledge on the molecular understandingof T-PLL’s pathobiology and critically assess the true translational progress around this tohelp appraisal by caregivers and patients. Overall, the contemporary concepts on T-PLL’spathobiology are condensed in a comprehensive mechanistic disease model andpromising interventional strategies derived from it are highlighted.
  • Zugangsstatus: Freier Zugang
  • Rechte-/Nutzungshinweise: Namensnennung (CC BY)