miRNA Signature in Early-stage Mycosis Fungoides


  • Sissel T. Sørensen
  • Thomas Litman
  • Maria Gluud
  • Pamela Celis
  • Sara Torres-Rusillo
  • Andreas Willerslev-Olsen
  • Niels Ødum
  • Lars Iversen
  • Lise M. Lindahl Department of Dermatology, Aarhus University Hospital, Palle Juul-Jensens Blvd 99, DK-8200 Aarhus N, Denmark




mycosis fungoides, cutaneous T-cell lymphoma, microRNA, cancer


Altered miRNA expressions are assigned pathogenic properties in several cancers including mycosis fungoides and could play a role in the early onset of the disease. The aim of this study was to examine disease-specific miRNA expression in early-stage mycosis fungoides patch and plaque lesions. A quantitative real-time PCR platform of 384 human miRNAs was used to study miRNA expression in 154 diagnostic mycosis fungoides biopsies. A total of 110 miRNAs were significantly differentially expressed (>2-fold, p < 0.05) between plaque lesions and healthy controls, and 90 miRNAs (>2-fold, p < 0.05) differed between patch lesions and healthy controls. Moreover, 13 miRNAs differed in expression between patch and plaque lesions. Early-stage mycosis fungoides exhibited miRNA features that overlapped with those of psoriasis. However, 39 miRNAs, including miR-142-3p, miR-150 and miR-146b, were specific to mycosis fungoides. In conclusion, early-stage mycosis fungoides expresses a distinct miRNA profile, indicating that miRNAs could play a role in the early development of mycosis fungoides.


Download data is not yet available.


Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood 2009; 113: 5064-5073.

https://doi.org/10.1182/blood-2008-10-184168 DOI: https://doi.org/10.1182/blood-2008-10-184168

Ahn CS, A AL, Sangueza OP. Mycosis fungoides: an updated review of clinicopathologic variants. Am J Dermatopathol 2014; 36: 933-948; quiz 949-951.

https://doi.org/10.1097/DAD.0000000000000207 DOI: https://doi.org/10.1097/DAD.0000000000000207

Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105: 3768-3785.

https://doi.org/10.1182/blood-2004-09-3502 DOI: https://doi.org/10.1182/blood-2004-09-3502

Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, et al. Defining early mycosis fungoides. J Am Acad Dermatol 2005; 53: 1053-1063.

https://doi.org/10.1016/j.jaad.2005.08.057 DOI: https://doi.org/10.1016/j.jaad.2005.08.057

Agar NS, Wedgeworth E, Crichton S, Mitchell TJ, Cox M, Ferreira S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sezary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 2010; 28: 4730-4739.

https://doi.org/10.1200/JCO.2009.27.7665 DOI: https://doi.org/10.1200/JCO.2009.27.7665

MacKie RM. Initial event in mycosis fungoides of the skin is viral infection of epidermal Langerhans cells. Lancet 1981; 2: 283-285.

https://doi.org/10.1016/S0140-6736(81)90529-8 DOI: https://doi.org/10.1016/S0140-6736(81)90529-8

Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Bonefeld CM, Wasik MA, Koralov SB, et al. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma. Toxins (Basel) 2013; 5: 1402-1421.

https://doi.org/10.3390/toxins5081402 DOI: https://doi.org/10.3390/toxins5081402

Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Litvinov IV, Fredholm S, Petersen DL, et al. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma. Blood 2016; 127: 1287-1296.

https://doi.org/10.1182/blood-2015-08-662353 DOI: https://doi.org/10.1182/blood-2015-08-662353

Krejsgaard T, Willerslev-Olsen A, Lindahl LM, Bonefeld CM, Koralov SB, Geisler C, et al. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation. Blood 2014; 124: 761-770.

https://doi.org/10.1182/blood-2014-01-551184 DOI: https://doi.org/10.1182/blood-2014-01-551184

Jackow CM, Cather JC, Hearne V, Asano AT, Musser JM, Duvic M. Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion. Blood 1997; 89: 32-40.

https://doi.org/10.1182/blood.V89.1.32.32_32_40 DOI: https://doi.org/10.1182/blood.V89.1.32.32_32_40

Talpur R, Bassett R, Duvic M. Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sezary syndrome. Br J Dermatol 2008; 159: 105-112.

https://doi.org/10.1111/j.1365-2133.2008.08612.x DOI: https://doi.org/10.1111/j.1365-2133.2008.08612.x

Lindahl LM, Willerslev-Olsen A, Gjerdrum LMR, Nielsen PR, Blumel E, Rittig AH, et al. Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma. Blood 2019; 134: 1072-1083.

https://doi.org/10.1182/blood.2018888107 DOI: https://doi.org/10.1182/blood.2018888107

Odum N, Lindahl LM, Wod M, Krejsgaard T, Skytthe A, Woetmann A, et al. Investigating heredity in cutaneous T-cell lymphoma in a unique cohort of Danish twins. Blood Cancer J 2017; 7: e517.

https://doi.org/10.1038/bcj.2016.128 DOI: https://doi.org/10.1038/bcj.2016.128

Litvinov IV, Tetzlaff MT, Thibault P, Gangar P, Moreau L, Watters AK, et al. Gene expression analysis in cutaneous T-cell lymphomas (CTCL) highlights disease heterogeneity and potential diagnostic and prognostic indicators. Oncoimmunology 2017; 6: e1306618.

https://doi.org/10.1080/2162402X.2017.1306618 DOI: https://doi.org/10.1080/2162402X.2017.1306618

Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, et al. Genomic landscape of cutaneous T cell lymphoma. Nat Genet 2015; 47: 1011-1019.

https://doi.org/10.1038/ng.3356 DOI: https://doi.org/10.1038/ng.3356

Lindahl LM, Fredholm S, Joseph C, Nielsen BS, Jonson L, Willerslev-Olsen A, et al. STAT5 induces miR-21 expression in cutaneous T cell lymphoma. Oncotarget 2016; 7: 45730-45744.

https://doi.org/10.18632/oncotarget.10160 DOI: https://doi.org/10.18632/oncotarget.10160

Sibbesen NA, Kopp KL, Litvinov IV, Jonson L, Willerslev-Olsen A, Fredholm S, et al. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget 2015; 6: 20555-20569.

https://doi.org/10.18632/oncotarget.4111 DOI: https://doi.org/10.18632/oncotarget.4111

Lindahl LM, Besenbacher S, Rittig AH, Celis P, Willerslev-Olsen A, Gjerdrum LMR, et al. Prognostic miRNA classifier in early-stage mycosis fungoides: development and validation in a Danish nationwide study. Blood 2018; 131: 759-770.

https://doi.org/10.1182/blood-2017-06-788950 DOI: https://doi.org/10.1182/blood-2017-06-788950

Ralfkiaer U, Hagedorn PH, Bangsgaard N, Lovendorf MB, Ahler CB, Svensson L, et al. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood 2011; 118: 5891-5900.

https://doi.org/10.1182/blood-2011-06-358382 DOI: https://doi.org/10.1182/blood-2011-06-358382

van Kester MS, Ballabio E, Benner MF, Chen XH, Saunders NJ, van der Fits L, et al. miRNA expression profiling of mycosis fungoides. Mol Oncol 2011; 5: 273-280.

https://doi.org/10.1016/j.molonc.2011.02.003 DOI: https://doi.org/10.1016/j.molonc.2011.02.003

Ballabio E, Mitchell T, van Kester MS, Taylor S, Dunlop HM, Chi J, et al. MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential. Blood 2010; 116: 1105-1113.

https://doi.org/10.1182/blood-2009-12-256719 DOI: https://doi.org/10.1182/blood-2009-12-256719

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297.

https://doi.org/10.1016/S0092-8674(04)00045-5 DOI: https://doi.org/10.1016/S0092-8674(04)00045-5

Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006; 6: 259-269.

https://doi.org/10.1038/nrc1840 DOI: https://doi.org/10.1038/nrc1840

Ralfkiaer U, Lindahl LM, Litman T, Gjerdrum LM, Ahler CB, Gniadecki R, et al. MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma. Anticancer Res 2014; 34: 7207-7217.

Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007; 110: 1713-1722.

https://doi.org/10.1182/blood-2007-03-055749 DOI: https://doi.org/10.1182/blood-2007-03-055749

Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet 2012; 13: 358-369.

https://doi.org/10.1038/nrg3198 DOI: https://doi.org/10.1038/nrg3198

Islam F, Gopalan V, Vider J, Lu CT, Lam AK. MiR-142-5p act as an oncogenic microRNA in colorectal cancer: clinicopathological and functional insights. Exp Mol Pathol 2018; 104: 98-107.

https://doi.org/10.1016/j.yexmp.2018.01.006 DOI: https://doi.org/10.1016/j.yexmp.2018.01.006

Xu W, Wang W. MicroRNA1425p modulates breast cancer cell proliferation and apoptosis by targeting phosphatase and tensin homolog. Mol Med Rep 2018; 17: 7529-7536.

https://doi.org/10.3892/mmr.2018.8812 DOI: https://doi.org/10.3892/mmr.2018.8812

Liu L, Liu S, Duan Q, Chen L, Wu T, Qian H, et al. MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3. Am J Transl Res 2017; 9: 2394-2402.

Aucher A, Rudnicka D, Davis DM. MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. J Immunol 2013; 191: 6250-6260.

https://doi.org/10.4049/jimmunol.1301728 DOI: https://doi.org/10.4049/jimmunol.1301728

Sandoval J, Diaz-Lagares A, Salgado R, Servitje O, Climent F, Ortiz-Romero PL, et al. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma. J Invest Dermatol 2015; 135: 1128-1137.

https://doi.org/10.1038/jid.2014.487 DOI: https://doi.org/10.1038/jid.2014.487

Cristofoletti C, Picchio MC, Lazzeri C, Tocco V, Pagani E, Bresin A, et al. Comprehensive analysis of PTEN status in Sezary syndrome. Blood 2013; 122: 3511-3520.

https://doi.org/10.1182/blood-2013-06-510578 DOI: https://doi.org/10.1182/blood-2013-06-510578

Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 2010; 39: 493-506.

https://doi.org/10.1016/j.molcel.2010.07.023 DOI: https://doi.org/10.1016/j.molcel.2010.07.023

Kadera BE, Li L, Toste PA, Wu N, Adams C, Dawson DW, et al. MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One 2013; 8: e71978.

https://doi.org/10.1371/journal.pone.0071978 DOI: https://doi.org/10.1371/journal.pone.0071978

Bullock MD, Pickard KM, Nielsen BS, Sayan AE, Jenei V, Mellone M, et al. Pleiotropic actions of miR-21 highlight the critical role of deregulated stromal microRNAs during colorectal cancer progression. Cell Death Dis 2013; 4: e684-e684.

https://doi.org/10.1038/cddis.2013.213 DOI: https://doi.org/10.1038/cddis.2013.213

Wang J, Li Y, Ding M, Zhang H, Xu X, Tang J. Molecular mechanisms and clinical applications of miR-22 in regulating malignant progression in human cancer (Review). Int J Oncol 2017; 50: 345-355.

https://doi.org/10.3892/ijo.2016.3811 DOI: https://doi.org/10.3892/ijo.2016.3811

Song SJ, Pandolfi PP. MicroRNAs in the pathogenesis of myelodysplastic syndromes and myeloid leukaemia. Curr Opin Hematol 2014; 21: 276-282.

https://doi.org/10.1097/MOH.0000000000000054 DOI: https://doi.org/10.1097/MOH.0000000000000054

Wu H, Liu J, Zhang Y, Li Q, Wang Q, Gu Z. miR-22 suppresses cell viability and EMT of ovarian cancer cells via NLRP3 and inhibits PI3K/AKT signaling pathway. Clin Transl Oncol 2021; 23: 257-264.

https://doi.org/10.1007/s12094-020-02413-8 DOI: https://doi.org/10.1007/s12094-020-02413-8

Gluud M, Willerslev-Olsen A, Gjerdrum LMR, Lindahl LM, Buus TB, Andersen MH, et al. MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas. Cancers (Basel) 2020; 12: 1229.

https://doi.org/10.3390/cancers12051229 DOI: https://doi.org/10.3390/cancers12051229

Løvendorf MB, Zibert JR, Hagedorn PH, Glue C, Ødum N, Røpke MA, et al. Comparison of microRNA expression using different preservation methods of matched psoriatic skin samples. Exp Dermatol 2012; 21: 299-301.

https://doi.org/10.1111/j.1600-0625.2012.01445.x DOI: https://doi.org/10.1111/j.1600-0625.2012.01445.x



How to Cite

Sørensen, S. T., Litman, T. ., Gluud, M. ., Celis, P., Torres-Rusillo, S. ., Willerslev-Olsen, A. ., Ødum, N., Iversen, L. ., & Lindahl, L. M. (2022). miRNA Signature in Early-stage Mycosis Fungoides. Acta Dermato-Venereologica, 102, adv00785. https://doi.org/10.2340/actadv.v102.628