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Neues zu Pathogenese und molekularem Verständnis bei kutanen T-Zell-Lymphomen

New insights into the pathogenesis and molecular understanding of cutaneous T-cell lymphomas

Zusammenfassung

Die Pathogenese der kutanen T‑Zell-Lymphome (KTZL) ist nach wie vor ein Enigma. Daher wurden gerade in den letzten Jahren umfangreiche translationale Forschungsanstrengungen unternommen, um zu weitergehenden klinischen und molekularen Erkenntnissen zu gelangen. Es gibt zunehmend Hinweise darauf, dass das unterschiedliche klinische Erscheinungsbild der KTZL-Subtypen darauf zurückzuführen ist, dass sie von verschiedenen hautständigen Subpopulationen von T‑Zellen abstammen. Der Nachweis und die Quantifizierung der bösartigen T‑Zell-Klone sind entscheidend für die Diagnose und Prognose von KTZL. Es wurden in den letzten Jahren zahlreiche wiederkehrend mutierte zelluläre Signalwege gefunden. Das beinhaltet JAK(Januskinase)-STAT(„signal transducers and activators of transcription“)-, NF-κB(„nuclear factor kappa B“)-, T‑Zell-Rezeptor- und MAP(„mitogen-activated protein“)-Kinase-Signalwege sowie die Zellzykluskontrolle und Epigenetik. Die jüngsten Analysen implizieren ein Tumorevolutionsmodell mit anfänglichen Kopienzahlvariationen wie Amplifikationen oder Deletionen bestimmter DNA(Desoxyribonukleinsäure)-Abschnitte („copy number variations“ [CNVs]) und erst darauffolgenden späteren Einzelnukleotidvariationen („single nucleotide variations“ [SNVs]). Die entscheidende Frage ist jedoch, welche CNVs ausreichen, um eine generelle Tumorgenese zu beginnen. Die Herausforderung ist, mögliche Treibergene zu identifizieren. Das zunehmende molekulare Verständnis bei KTZL wird in naher Zukunft neue bahnbrechende Therapieoptionen beinhalten.

Abstract

The pathogenesis of cutaneous T‑cell lymphomas (CTCL) is still an enigma. Therefore, extensive translational research efforts have been undertaken in recent years to gain further clinical and molecular insights. There is increasing evidence that the different clinical appearance of the CTCL subtypes derives from the assumption that they develop from different skin subpopulations of T cells. Detection and quantification of the malignant T‑cell clones is crucial for the diagnosis and prognosis of CTCL. Numerous recurrent mutant cellular signalling pathways have been found in recent years. This includes the JAK-STAT, NFκB, T‑cell receptor and MAP kinase signalling pathways, as well as cell cycle control and epigenetics. The most recent analyses imply a tumour evolution model with initial copy number variation, like amplification or deletions of specific DNA fragments (CNVs) and only subsequent later single nucleotide variations (SNVs). The crucial question, however, is which CNVs are sufficient to initiate general tumourigenesis? The challenge is to identify possible driver genes. Increasing molecular understanding in CTCL will include new breakthrough therapeutic options in the near future.

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Correspondence to Rudolf Stadler.

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R. Stadler und C. Hain geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Stadler, R., Hain, C. Neues zu Pathogenese und molekularem Verständnis bei kutanen T-Zell-Lymphomen. Dermatologie 73, 765–771 (2022). https://doi.org/10.1007/s00105-022-05047-9

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  • DOI: https://doi.org/10.1007/s00105-022-05047-9

Schlüsselwörter

  • Molekulare Diagnostik
  • T‑Zellen
  • T-Zell-Lymphome
  • Zelluläre Signalwege
  • Zielgerichtete Therapie
  • Tumorgenese
  • Treibergene

Keywords

  • Molecular diagnostics
  • T cells
  • T-cell lymphoma
  • Cellular signalling pathways
  • Targeted therapy
  • Tumorigenesis
  • Driver genes