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Unilesional mycosis fungoides is associated with increased expression of micro RNA ‐17~92 and T helper 1 skewing
Author(s) -
Moyal L.,
GorovitzHaris B.,
Yehezkel S.,
JacobHirsch J.,
Bershtein V.,
Barzilai A.,
Rotem C.,
Sherman S.,
AmitayLaish I.,
Feinmesser M.,
Hodak E.
Publication year - 2019
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.17425
Subject(s) - mycosis fungoides , tensin , gata3 , pten , biology , microrna , immune system , cxcr3 , immunology , pathology , microbiology and biotechnology , medicine , chemokine , gene , lymphoma , apoptosis , pi3k/akt/mtor pathway , chemokine receptor , transcription factor , biochemistry
Summary Background The molecular basis of unilesional mycosis fungoides ( MF ), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF ), is unknown. Objectives To investigate the micro RNA profile in unilesional MF distinguishing it from early MF . Methods Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix micro RNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR 3 and GATA ‐binding protein 3 ( GATA 3) markers for Th1 and Th2 cells, respectively. Results Unilesional MF had a significantly higher level of expression of all members of the micro RNA miR‐17~92 cluster than early MF . Specifically, unilesional MF had a higher miR‐17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog ( PTEN ) and CREB 1, known targets of miR‐17~92 members; higher gene expression of interleukin‐2 and interferon‐γ; and a statistically lower average percentage of GATA 3 + dermal cells (6·7% vs. 42·3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR 3 was noted in both unilesional and early MF . Conclusions Unilesional MF exhibits a micro RNA profile distinct from that of conventional early MF , with a higher level of miR‐17~92 members along with Th1 skewing. These findings suggest a robust reactive T‐cell immune response in unilesional MF and might account for the localized nature of this disease.