title: MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma.
abstract: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphoma (CTCL). MF is characterized by chronic inflammation dominated by cluster of differentiation 4-positive (CD4(+)) T-cells and T helper 2 cytokines, and as the malignant T-cell clone is initially elusive, early diagnosis is often impossible. MF usually takes an indolent course, but for unknown reasons may turn into an aggressive disease with a poor prognosis. Herein, we used a global quantitative real-time polymerase chain reaction platform to study microRNA (miR) expression in patients with early MF (n=13), more advanced CTCL (n=42), and atopic dermatitis (AD, n=20). Thirty-eight miRs were differentially expressed (≥2-fold) in early MF vs. AD and 36 in early MF vs. more advanced disease. miRs that distinguish early MF from AD included both up-regulated (miR-155, miR-146a, 146b-5p, miR-342-3p, let-7i*) and down-regulated (miR-203, miR-205) miRs previously implicated in advanced CTCL. When comparing early MF to more advanced CTCL, additional miRs were significantly up-regulated including miRs which are part of the oncogenic miR-17/92, 106b/25 and 106a/363 clusters. In 16 patients for whom detailed follow-up data were available, 72 miRs were found differentially expressed between patients with progressive vs. those with non-progressive disease, again including miRs with a known relevance for lymphomagenesis, e.g. miR-155, miR-21, let-7i, miR-16, miR-142-3p, miR-146b-5p, miR-92a, miR-93 and miR-106a. In conclusion, we showed that early MF and AD display very different miR profiles despite their clinical, histological, and immunological similarities. During progression, an additional set of miRs becomes deregulated, suggesting their role in disease progression. These data suggest that miR profiling in CTCL may be a key to improving both diagnosis and risk prediction.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lise M
authors.initials: LM
authors.lastname: Lindahl
authors.forename: Lise
authors.initials: L
authors.lastname: Lindal
authors.affiliation: Leo-Pharma, Ballerup, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Lise-Mette
authors.initials: LM
authors.lastname: Gjerdrum
authors.affiliation: Leo-Pharma, Ballerup, Denmark.
authors.forename: Charlotte Busch
authors.initials: CB
authors.lastname: Ahler
authors.affiliation: Department of Dermatology, Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.affiliation: Leo-Pharma, Ballerup, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Marstrand
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Fredholm
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, U.S.A.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.affiliation: Exiqon A/S, Vedbaek, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Glue
authors.affiliation: Leo-Pharma, Ballerup, Denmark.
authors.forename: Mads Almose
authors.initials: MA
authors.lastname: Røpke
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
authors.affiliation: Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark ndum@sund.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009182:Mycosis Fungoides / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Cutaneous T-cell lymphoma (CTCL); diagnosis; microRNA; mycosis fungoides