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Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma

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  1. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Overall Survival in Mycosis Fungoides: A Systematic Review and Meta-Analysis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Patient-reported Outcomes During Treatment in Patients with Moderate-to-severe Psoriasis: A Danish Nationwide Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Aishwarya Iyer
  • Dylan Hennessey
  • Sandra O'Keefe
  • Jordan Patterson
  • Weiwei Wang
  • Gane Ka-Shu Wong
  • Robert Gniadecki
Vis graf over relationer

Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, β, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind134
Udgave nummer18
Sider (fra-til)1517-1527
Antal sider11
ISSN0006-4971
DOI
StatusUdgivet - 31 okt. 2019

Bibliografisk note

© 2019 by The American Society of Hematology.

ID: 59268043