MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma

Ulrik Ralfkiaer; Lise M Lindahl; Thomas Litman; Lise-Mette Gjerdrum; Charlotte Busch Ahler; Robert Gniadecki; Troels Marstrand; Simon Fredholm; Lars Iversen; Mariusz A Wasik; Charlotte M Bonefeld; Carsten Geisler; Thorbjørn Krejsgaard; Christian Glue; Mads Almose Røpke; Anders Woetmann; Lone Skov; Kirsten Grønbæk; Niels Odum

MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma

Ulrik Ralfkiaer, Lise M Lindahl, Thomas Litman, Lise-Mette Gjerdrum, Charlotte Busch Ahler, Robert Gniadecki, Troels Marstrand, Simon Fredholm, Lars Iversen, Mariusz A Wasik, Charlotte M Bonefeld, Carsten Geisler, Thorbjørn Krejsgaard, Christian Glue, Mads Almose Røpke, Anders Woetmann, Lone Skov, Kirsten Grønbæk, Niels Odum

49 Citations (Scopus)

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.

Original language	English
Journal	Anticancer Research
Volume	34
Issue number	12
Pages (from-to)	7207-17
Number of pages	11
ISSN	0250-7005
Publication status	Published - 1 Dec 2014

Keywords

Dermatitis, Atopic
Disease Progression
Humans
Lymphoma, T-Cell, Cutaneous
MicroRNAs
Mycosis Fungoides
Polymerase Chain Reaction
Skin Neoplasms
Th2 Cells
Tumor Markers, Biological

Cite this

Ralfkiaer, U., Lindahl, L. M., Litman, T., Gjerdrum, L.-M., Ahler, C. B., Gniadecki, R., Marstrand, T., Fredholm, S., Iversen, L., Wasik, M. A., Bonefeld, C. M., Geisler, C., Krejsgaard, T., Glue, C., Røpke, M. A., Woetmann, A., Skov, L., Grønbæk, K., & Odum, N. (2014). MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma. Anticancer Research, 34(12), 7207-17.

Ralfkiaer, U, Lindahl, LM, Litman, T , Gjerdrum, L-M, Ahler, CB, Gniadecki, R, Marstrand, T, Fredholm, S, Iversen, L, Wasik, MA, Bonefeld, CM, Geisler, C, Krejsgaard, T, Glue, C, Røpke, MA, Woetmann, A, Skov, L , Grønbæk, K & Odum, N 2014, 'MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma', Anticancer Research, vol. 34, no. 12, pp. 7207-17.

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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.",

keywords = "Dermatitis, Atopic, Disease Progression, Humans, Lymphoma, T-Cell, Cutaneous, MicroRNAs, Mycosis Fungoides, Polymerase Chain Reaction, Skin Neoplasms, Th2 Cells, Tumor Markers, Biological",

author = "Ulrik Ralfkiaer and Lindahl, {Lise M} and Thomas Litman and Lise-Mette Gjerdrum and Ahler, {Charlotte Busch} and Robert Gniadecki and Troels Marstrand and Simon Fredholm and Lars Iversen and Wasik, {Mariusz A} and Bonefeld, {Charlotte M} and Carsten Geisler and Thorbj{\o}rn Krejsgaard and Christian Glue and R{\o}pke, {Mads Almose} and Anders Woetmann and Lone Skov and Kirsten Gr{\o}nb{\ae}k and Niels Odum",

year = "2014",

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day = "1",

language = "English",

volume = "34",

pages = "7207--17",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "12",

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TY - JOUR

T1 - MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma

AU - Ralfkiaer, Ulrik

AU - Lindahl, Lise M

AU - Litman, Thomas

AU - Gjerdrum, Lise-Mette

AU - Ahler, Charlotte Busch

AU - Gniadecki, Robert

AU - Marstrand, Troels

AU - Fredholm, Simon

AU - Iversen, Lars

AU - Wasik, Mariusz A

AU - Bonefeld, Charlotte M

AU - Geisler, Carsten

AU - Krejsgaard, Thorbjørn

AU - Glue, Christian

AU - Røpke, Mads Almose

AU - Woetmann, Anders

AU - Skov, Lone

AU - Grønbæk, Kirsten

AU - Odum, Niels

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

KW - Dermatitis, Atopic

KW - Disease Progression

KW - Humans

KW - Lymphoma, T-Cell, Cutaneous

KW - MicroRNAs

KW - Mycosis Fungoides

KW - Polymerase Chain Reaction

KW - Skin Neoplasms

KW - Th2 Cells

KW - Tumor Markers, Biological

M3 - Journal article

C2 - 25503151

SN - 0250-7005

VL - 34

SP - 7207

EP - 7217

JO - Anticancer Research

JF - Anticancer Research

IS - 12

ER -

MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma

Abstract

Keywords

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