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The cross-talk between miRNAs and JAK/STAT pathway in cutaneous T cell lymphoma: Emphasis on therapeutic opportunities

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journal contribution
submitted on 2023-11-13, 09:49 and posted on 2023-11-13, 10:12 authored by Kalyani Patil, Gulab Sher, Shilpa Kuttikrishnan, Safwan Moton, Majid Alam, Joerg Buddenkotte, Aamir Ahmad, Martin Steinhoff, Shahab Uddin

Mycosis Fungoides (MF) and Sézary Syndrome (SS) belong to a wide spectrum of T cell lymphoproliferative disorders collectively termed cutaneous T cell lymphomas (CTCL). CTCLs represent an archetype of heterogeneous and dynamically variable lymphoproliferative neoplasms typified by distinct clinical, histological, immunophenotypic, and genetic features. Owing to its complex dynamics, the pathogenesis of CTCL remains elusive. However, in recent years, progress in CTCL classification combined with next-generation sequencing analyses has broadened the genetic and epigenetic spectrum of clearly defined CTCL entities such as MF and SS. Several large-scale genome studies have identified the polygenic nature of CTCL and unveiled an idiosyncratic mutational landscape involving genetic aberrations, epigenetic alterations, cell cycle dysregulation, apoptosis, and the constitutive activation of T cell/NF-κB/JAK-STAT signaling pathways. In this review, we summarize the evolving insights on how the intrinsic epigenetic events driven by dysregulated miRNAs, including the oncogenic and tumor-suppressive miRNAs, influence the pathogenesis of MF and SS. We also focus on the interplay between the JAK/STAT pathway and miRNAs in CTCL as well as the significance of the miRNA/STAT axis as a relevant pathogenetic mechanism underlying CTCL initiation and progression. Based on these biologic insights, the current status and recent progress on novel therapies with a strong biological rationale, including miRNA-targeted molecules and JAK/STAT-targeted therapy for CTCL management, are discussed.

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Published in: Seminars in Cell & Developmental Biology
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2024

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Interim Translational Research Institute - HMC
  • Dermatology Institute - HMC
  • Rumailah Hospital - HMC
  • Weill Cornell Medicine - Qatar
  • Qatar University
  • Laboratory Animal Research Center - QU