jsmsJournal of Siberian Medical SciencesJournal of Siberian Medical Sciences2542-1174Federal state budgetary educational institution of higher education "Novosibirsk state medical university" of Ministry of Health of the Russian Federation (FSBEI HE NSMU MOH Russia)10.31549/2542-1174-2024-8-4-116-129jsms-1108Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПрофиль экспрессии микроРНК в диагностическом субстрате первичной кожной Т-клеточной неходжкинской лимфомыMicroRNA expression profile in the diagnostic substrate of primary cutaneous T cell non-Hodgkin’s lymphomahttps://orcid.org/0000-0002-3799-9407ВеряскинаЮ. А.VeryaskinaYu A.

Веряскина Юлия Андреевна – канд. биол. наук, старший научный сотрудник лаборатории молекулярной генетики

630090, г. Новосибирск, просп. акад. Лаврентьева, 8/2

Yulia A. Veryaskina – Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Genetics

8/2, Acad. Lavrentiev Ave., Novosibirsk,  630090

КовыневИ. Б.KovynevI. B.

Ковынев Игорь Борисович – д-р мед. наук, доцент кафедры терапии, гематологии и трансфузиологии

Новосибирск

Igor B. Kovynev – Dr. Sci. (Med.), Associate Professor, Department of Therapy, Hematology and Transfusiology

Novosibirsk

ПахомоваВ. В.PakhomovaV. V.

Пахомова Вера Владимировна – заместитель главного врача по медицинской части, врач-дерматовенеролог

Новосибирск

Vera V. Pakhomova – Deputy Chief Physician for Medical Affairs, Dermatovenereologist

Novosibirsk

ТитовС. Е.TitovS. E.

Титов Сергей Евгеньевич – канд. биол. наук, старший научный сотрудник лаборатории молекулярной генетики

Новосибирск

Sergey E. Titov – Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Genetics; Senior Researcher

Novosibirsk

ВойткоМ. С.VoitkoM. S.

Войтко Мария Сергеевна – канд. мед. наук, ассистент кафедры терапии, гематологии и трансфузиологии

Новосибирск

Maria S. Voitko – Cand. Sci. (Med.), Assistant Professor, Department of Therapy, Hematology and Transfusiology

Novosibirsk

ЦигулёвК. С.TsigulevK. S.

Цигулёв Константин Сергеевич – студент 6-го курса

Новосибирск

Konstantin S. Tsigulev – 6-year Student

Novosibirsk

ОнипченкоВ. В.OnipchenkoV. V.

Онипченко Вера Викторовна – главный внештатный специалист по дерматовенерологии и косметологии

Новосибирск

Vera V. Onipchenko – Chief Non-staff  Specialist on Dermatovenereology and Cosmetology of the Novosibirsk Region, Chief Physician

Novosibirsk

ФГБУН «Институт молекулярной и клеточной биологии Сибирского отделения Российской академии наук»РоссияInstitute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of SciencesRussian FederationФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian FederationГБУЗ НСО «Новосибирский областной клинический кожно-венерологический диспансер»РоссияNovosibirsk Regional Clinical Skin and Venereal Diseases DispensaryRussian FederationФГБУН «Институт молекулярной и клеточной биологии Сибирского отделения Российской академии наук»; АО «Вектор-Бест»РоссияInstitute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences; Vector-BestRussian Federation20241812202484116129Copyright © Веряскина Ю.А., Ковынев И.Б., Пахомова В.В., Титов С.Е., Войтко М.С., Цигулёв К.С., Онипченко В.В., 20242024Веряскина Ю.А., Ковынев И.Б., Пахомова В.В., Титов С.Е., Войтко М.С., Цигулёв К.С., Онипченко В.В.Veryaskina Y.A., Kovynev I.B., Pakhomova V.V., Titov S.E., Voitko M.S., Tsigulev K.S., Onipchenko V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://jsms.elpub.ru/jour/article/view/1108В в е д е н и е

В в е д е н и е . Первичные Т-клеточные лимфомы кожи (ТКЛК) представляют собой гетерогенную группу экстранодальных неходжкинских лимфом, которые на момент постановки диагноза локально ограничиваются кожей. Диагностика ТКЛК часто затруднена, поскольку на определенных этапах развития этого гемобластоза имеются клинические сходства с такими неопухолевыми дерматологическими заболеваниями, как хронический экзематозный дерматит, псориаз, красный волосяной лишай или грибковые инфекции. В патогенезе ТКЛК участвуют как генетические, так и эпигенетические факторы, в частности, микроРНК (миРНК).

Ц е л ь

Ц е л ь . Выявление миРНК, позволяющих дифференцировать ТКЛК от доброкачественных образований (ДО) кожи, и определение их роли в генетических путях, участвующих в развитии ТКЛК.

М а т е р и а л ы и м е т о д ы . Методом ПЦР с обратной транскрипцией в реальном времени проведен анализ уровней экспрессии миРНК-181а, -155, -574, -148b, -191, -26а, -21, -124, -221, -200b, -20а, -92а, -145, let-7a и let-7d в 5 фиксированных формалином и залитых парафином образцах биопсии кожи пациентов с диагнозом «ТКЛК», а также 20 образцах биопсии кожи пациентов с диагнозом «псориаз» (контрольная группа).

Р е з у л ь т а т ы

Р е з у л ь т а т ы . Сравнительный анализ уровней экспрессии миРНК между образцами ТКЛК и ДО показал статистически значимое увеличение уровней миРНК-181а, -155, -574, -148b и -191 в опухолевых образцах (p < 0.05). В ходе ROC-анализа установлено, что миРНК-155 и миРНК-181а являются высокочувствительными и специфичными маркерами для диагностики ТКЛК.

З а к л ю ч е н и е

З а к л ю ч е н и е . Анализ уровней экспрессии миРНК может быть перспективным инструментом для дифференциальной диагностики дерматотропных лимфоидных гемобластозов и негемопоэтических болезней кожи.

I n t r o d u c t i o n

I n t r o d u c t i o n . Primary cutaneous T cell lymphomas (CTCL) are a heterogeneous group of extranodal nonHodgkin’s lymphomas that are locally limited to the skin at diagnosis. The diagnosis of CTCL is often diffi  cult, since at certain stages of development, this hematological malignancy has clinical similarities with non-neoplastic dermatological diseases such as chronic eczematous dermatitis, psoriasis, lichen ruber, or fungal infections. Both genetic and epigenetic factors, in particular microRNAs (miRNAs), are involved in the pathogenesis of CTCL.

A i m

A i m . To identify the miRNAs that diff erentiate CTCL from benign skin lesions (BSL) and determine their role in genetic pathways involved in the development of CTCL.

M a t e r i a l s a n d m e t h o d s . Real-time reverse transcription PCR was used to analyze the expression levels of miRNA-181a, -155, -574, -148b, -191, -26a, -21, -124, -221, -200b, -20a, -92a, -145, let-7a, and let-7d in 5 formalin-fi xed paraffi  n-embedded skin biopsy samples from patients with CTCL and 20 skin biopsy samples from patients with psoriasis (control group).

R e s u l t s

R e s u l t s . Comparative analysis of miRNA expression levels between CTCL and BSL samples showed a statistically signifi cant increase in the levels of miRNA-181a, -155, -574, -148b and -191 in tumor samples (p < 0.05). ROC analysis showed that miRNA-155 and miRNA-181a are highly sensitive and specifi c markers for the diagnosis of CTCL.

C o n c l u s i o n

C o n c l u s i o n . Analysis of miRNA expression levels may be a promising tool for the diff erential diagnosis between dermatotropic lymphoid hematological malignancies and non-hematological skin diseases. 

микроРНКпервичные кожные Т-клеточные лимфомынеходжкинские лимфомыmicroRNAprimary cutaneous T cell lymphomasnon-Hodgkin’s lymphomasРабота выполнена при поддержке гранта Российского научного фонда № 24-25-20059 и Министерства науки и инновационной политики Новосибирской области по соглашению № р-76.ReferencesDobos G., Pohrt A., Ram-Wolff C. et al. Epidemiology of cutaneous T-cell lymphomas: a systematic review and meta-analysis of 16,953 patients // Cancers (Basel). 2020;12(10):2921. DOI: 10.3390/cancers12102921.Dobos G., Pohrt A., Ram-Wolff C. et al. Epidemiology of cutaneous T-cell lymphomas: a systematic review and meta-analysis of 16,953 patients // Cancers (Basel). 2020;12(10):2921. DOI: 10.3390/cancers12102921.Hristov A.C., Tejasvi T., Wilcox R.A. Cutaneous T-cell lymphomas: 2023 update on diagnosis, riskstratifi cation, and management // Am. J. Hematol. 2023;98(1):193-209. DOI: 10.1002/ajh.26760.Hristov A.C., Tejasvi T., Wilcox R.A. Cutaneous T-cell lymphomas: 2023 update on diagnosis, riskstratifi cation, and management // Am. J. Hematol. 2023;98(1):193-209. DOI: 10.1002/ajh.26760.Brunner P.M., Jonak C., Knobler R. Recent advances in understanding and managing cutaneous T-cell lymphomas // F1000Res. 2020;9(F1000 Faculty Rev):331. DOI: 10.12688/f1000research.21922.1.Brunner P.M., Jonak C., Knobler R. Recent advances in understanding and managing cutaneous T-cell lymphomas // F1000Res. 2020;9(F1000 Faculty Rev):331. DOI: 10.12688/f1000research.21922.1.Sokołowska-Wojdyło M., Olek-Hrab K., RuckemannDziurdzińska K. Primary cutaneous lymphomas: diagnosis and treatment // Postępy Dermatol. Alergol. 2015;32(5):368-383. DOI: 10.5114/pdia.2015.54749.Sokołowska-Wojdyło M., Olek-Hrab K., RuckemannDziurdzińska K. Primary cutaneous lymphomas: diagnosis and treatment // Postępy Dermatol. Alergol. 2015;32(5):368-383. DOI: 10.5114/pdia.2015.54749.Litvinov I.V., Tetzlaff M.T., Thibault P. et al. Gene expression analysis in Cutaneous T-Cell Lymphomas (CTCL) highlights disease heterogeneity and potential diagnostic and prognostic indicators // Oncoimmunology. 2017;6(5):e1306618. DOI: 10.1080/2162402X.2017.1306618.Litvinov I.V., Tetzlaff M.T., Thibault P. et al. Gene expression analysis in Cutaneous T-Cell Lymphomas (CTCL) highlights disease heterogeneity and potential diagnostic and prognostic indicators // Oncoimmunology. 2017;6(5):e1306618. DOI: 10.1080/2162402X.2017.1306618.Scott J., Lai C., Coltart G. et al. Coexistence of psoriasis and cutaneous T-cell lymphoma // Clin. Exp. Dermatol. 2023;48(10):1155-1159. DOI: 10.1093/ced/llad213.Scott J., Lai C., Coltart G. et al. Coexistence of psoriasis and cutaneous T-cell lymphoma // Clin. Exp. Dermatol. 2023;48(10):1155-1159. DOI: 10.1093/ced/llad213.Choi J., Goh G., Walradt T. et al. Genomic landscape of cutaneous T cell lymphoma // Nat. Genet. 2015;47(9):1011-1019. DOI: 10.1038/ng.3356.Choi J., Goh G., Walradt T. et al. Genomic landscape of cutaneous T cell lymphoma // Nat. Genet. 2015;47(9):1011-1019. DOI: 10.1038/ng.3356.Park J., Daniels J., Wartewig T. et al. Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity // Blood. 2021;138(14):1225-1236. DOI: 10.1182/blood.2020009655.Park J., Daniels J., Wartewig T. et al. Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity // Blood. 2021;138(14):1225-1236. DOI: 10.1182/blood.2020009655.Zhang Y., Wang Y., Yu R. et al. Molecular markers of early-stage mycosis fungoides // J. Invest. Dermatol. 2012;132(6):1698-1706. DOI: 10.1038/jid.2012.13.Zhang Y., Wang Y., Yu R. et al. Molecular markers of early-stage mycosis fungoides // J. Invest. Dermatol. 2012;132(6):1698-1706. DOI: 10.1038/jid.2012.13.Nebozhyn M., Loboda A., Kari L. et al. Quantitative PCR on 5 genes reliably identifi es CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy // Blood. 2006;107(8):3189-3196. DOI: 10.1182/blood2005-07-2813.Nebozhyn M., Loboda A., Kari L. et al. Quantitative PCR on 5 genes reliably identifi es CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy // Blood. 2006;107(8):3189-3196. DOI: 10.1182/blood2005-07-2813.Rassek K., Iżykowska K., Żurawek M. et al. TMEM244 gene expression as a potential blood diagnostic marker distinguishing Sézary syndrome from mycosis fungoides and benign erythroderma // J. Invest. Dermatol. 2023;143(2):344-347.e3. DOI: 10.1016/j.jid.2022.08.046.Rassek K., Iżykowska K., Żurawek M. et al. TMEM244 gene expression as a potential blood diagnostic marker distinguishing Sézary syndrome from mycosis fungoides and benign erythroderma // J. Invest. Dermatol. 2023;143(2):344-347.e3. DOI: 10.1016/j.jid.2022.08.046.Tensen C.P., Quint K.D., Vermeer M.H. Genetic and epigenetic insights into cutaneous T-cell lymphoma // Blood. 2022;139(1):15-33. DOI: 10.1182/blood.2019004256.Tensen C.P., Quint K.D., Vermeer M.H. Genetic and epigenetic insights into cutaneous T-cell lymphoma // Blood. 2022;139(1):15-33. DOI: 10.1182/blood.2019004256.Zhang P., Zhang M. Epigenetics in the pathogenesis and treatment of cutaneous T-cell lymphoma // Front. Oncol. 2021;11:663961. DOI: 10.3389/fonc.2021.663961.Zhang P., Zhang M. Epigenetics in the pathogenesis and treatment of cutaneous T-cell lymphoma // Front. Oncol. 2021;11:663961. DOI: 10.3389/fonc.2021.663961.Ralfkiaer U., Lindahl L.M., Litman T. et al. MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma // Anticancer Res. 2014;34(12):72077217. Erratum in: Anticancer Res. 2015;35(2):1219.Ralfkiaer U., Lindahl L.M., Litman T. et al. MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma // Anticancer Res. 2014;34(12):72077217. Erratum in: Anticancer Res. 2015;35(2):1219.Dusílková N., Bašová P., Polívka J. et al. Plasma miR-155, miR-203, and miR-205 are biomarkers for monitoring of primary cutaneous T-cell lymphomas// Int. J. Mol. Sci. 2017;18(10):2136. DOI: 10.3390/ijms18102136.Dusílková N., Bašová P., Polívka J. et al. Plasma miR-155, miR-203, and miR-205 are biomarkers for monitoring of primary cutaneous T-cell lymphomas// Int. J. Mol. Sci. 2017;18(10):2136. DOI: 10.3390/ijms18102136.Ralfkiaer U., Hagedorn P.H., Bangsgaard N. et al. Diagnostic microRNA profi ling in cutaneous T-cell lymphoma (CTCL) // Blood. 2011;118(22):5891-5900. DOI: 10.1182/blood-2011-06-358382.Ralfkiaer U., Hagedorn P.H., Bangsgaard N. et al. Diagnostic microRNA profi ling in cutaneous T-cell lymphoma (CTCL) // Blood. 2011;118(22):5891-5900. DOI: 10.1182/blood-2011-06-358382.Kotaki R., Koyama-Nasu R., Yamakawa N., Kotani A. miRNAs in normal and malignant hematopoiesis // Int. J. Mol. Sci. 2017;18(7):1495. DOI: 10.3390/ijms18071495.Kotaki R., Koyama-Nasu R., Yamakawa N., Kotani A. miRNAs in normal and malignant hematopoiesis // Int. J. Mol. Sci. 2017;18(7):1495. DOI: 10.3390/ijms18071495.Georgantas R.W. 3rd, Hildreth R., Morisot S. et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control // Proc. Natl. Acad. Sci. USA. 2007;104(8):2750-2755. DOI: 10.1073/pnas.0610983104.Georgantas R.W. 3rd, Hildreth R., Morisot S. et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control // Proc. Natl. Acad. Sci. USA. 2007;104(8):2750-2755. DOI: 10.1073/pnas.0610983104.Figueroa A.A., Fasano J.D., Martinez-Morilla S. et al. miR-181a regulates erythroid enucleation via the regulation of Xpo7 expression // Haematologica. 2018;103(8):e341-e344. DOI: 10.3324/haematol.2017.171785.Figueroa A.A., Fasano J.D., Martinez-Morilla S. et al. miR-181a regulates erythroid enucleation via the regulation of Xpo7 expression // Haematologica. 2018;103(8):e341-e344. DOI: 10.3324/haematol.2017.171785.Rodriguez A., Vigorito E., Clare S. et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-611. DOI: 10.1126/science.1139253.Rodriguez A., Vigorito E., Clare S. et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-611. DOI: 10.1126/science.1139253.Rodriguez A., Vigorito E., Clare S. et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-611. DOI: 10.1126/science.1139253.Rodriguez A., Vigorito E., Clare S. et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-611. DOI: 10.1126/science.1139253.Seddiki N., Brezar V., Ruffi n N. et al. Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology. 2014;142(1):32-38. DOI: 10.1111/imm.12227.Seddiki N., Brezar V., Ruffi n N. et al. Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology. 2014;142(1):32-38. DOI: 10.1111/imm.12227.Tan L.P., Wang M., Robertus J.L. et al. miRNA profi ling of B-cell subsets: specifi c miRNA profi le for germinal center B cells with variation between centroblasts and centrocytes. Lab. Invest. 2009;89(6):708-716. DOI: 10.1038/labinvest.2009.26.Tan L.P., Wang M., Robertus J.L. et al. miRNA profi ling of B-cell subsets: specifi c miRNA profi le for germinal center B cells with variation between centroblasts and centrocytes. Lab. Invest. 2009;89(6):708-716. DOI: 10.1038/labinvest.2009.26.Grigoryev Y.A., Kurian S.M., Hart T. et al. MicroRNA regulation of molecular networks mapped by global microRNA, mRNA, and protein expression in activated T lymphocytes. J. Immunol. 2011;187(5):2233-2243. DOI: 10.4049/jimmunol.1101233.Grigoryev Y.A., Kurian S.M., Hart T. et al. MicroRNA regulation of molecular networks mapped by global microRNA, mRNA, and protein expression in activated T lymphocytes. J. Immunol. 2011;187(5):2233-2243. DOI: 10.4049/jimmunol.1101233.Wu H., Neilson J.R., Kumar P. miRNA profi ling of naïve, eff ector and memory CD8 T cells. PLoS One. 2007;2(10):e1020. DOI: 10.1371/journal.pone.0001020.Wu H., Neilson J.R., Kumar P. miRNA profi ling of naïve, eff ector and memory CD8 T cells. PLoS One. 2007;2(10):e1020. DOI: 10.1371/journal.pone.0001020.Li Q.J., Chau J., Ebert P.J. et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007;129(1):147-161. DOI: 10.1016/j.cell.2007.03.008.Li Q.J., Chau J., Ebert P.J. et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007;129(1):147-161. DOI: 10.1016/j.cell.2007.03.008.Dudda J.C., Salaun B., Ji Y. et al. MicroRNA-155 is required for eff ector CD8+ T cell responses to virus infection and cancer. Immunity. 2013;38(4):742-753. DOI: 10.1016/j.immuni.2012.12.006.Dudda J.C., Salaun B., Ji Y. et al. MicroRNA-155 is required for eff ector CD8+ T cell responses to virus infection and cancer. Immunity. 2013;38(4):742-753. DOI: 10.1016/j.immuni.2012.12.006.Kim C., Ye Z., Weyand C.M., Goronzy J.J. miR-181aregulated pathways in T-cell diff erentiation and aging. Immun. Ageing. 2021;18(1):28. DOI: 10.1186/s12979021-00240-1.Kim C., Ye Z., Weyand C.M., Goronzy J.J. miR-181aregulated pathways in T-cell diff erentiation and aging. Immun. Ageing. 2021;18(1):28. DOI: 10.1186/s12979021-00240-1.Ben-Hamo R., Efroni S. MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype. Oncotarget. 2015;6(3):15941604. DOI: 10.18632/oncotarget.2734.Ben-Hamo R., Efroni S. MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype. Oncotarget. 2015;6(3):15941604. DOI: 10.18632/oncotarget.2734.Macfarlane L.A., Murphy P.R. MicroRNA: biogenesis, function and role in cancer. Curr. Genomics. 2010;11(7):537-561. DOI: 10.2174/138920210793175895.Macfarlane L.A., Murphy P.R. MicroRNA: biogenesis, function and role in cancer. Curr. Genomics. 2010;11(7):537-561. DOI: 10.2174/138920210793175895.Luongo F., Colonna F., Calapà F. et al. PTEN tumorsuppressor: the dam of stemness in cancer. Cancers (Basel). 2019;11(8):1076. DOI: 10.3390/cancers11081076.Luongo F., Colonna F., Calapà F. et al. PTEN tumorsuppressor: the dam of stemness in cancer. Cancers (Basel). 2019;11(8):1076. DOI: 10.3390/cancers11081076.Wang X., Huang H., Young K.H. The PTEN tumor suppressor gene and its role in lymphoma pathogenesis. Aging (Albany NY). 2015;7(12):1032-1049. DOI: 10.18632/aging.100855.Wang X., Huang H., Young K.H. The PTEN tumor suppressor gene and its role in lymphoma pathogenesis. Aging (Albany NY). 2015;7(12):1032-1049. DOI: 10.18632/aging.100855.Luchtel R.A. ETS1 function in leukemia and lymphoma. Adv. Exp. Med. Biol. 2024;1459:359-378. DOI: 10.1007/978-3-031-62731-6_16.Luchtel R.A. ETS1 function in leukemia and lymphoma. Adv. Exp. Med. Biol. 2024;1459:359-378. DOI: 10.1007/978-3-031-62731-6_16.Carpenter R.L., Lo H.W. STAT3 target genes relevant to human cancers. Cancers (Basel). 2014;6(2):897925. DOI: 10.3390/cancers6020897.Carpenter R.L., Lo H.W. STAT3 target genes relevant to human cancers. Cancers (Basel). 2014;6(2):897925. DOI: 10.3390/cancers6020897.Zhu F., Wang K.B., Rui L. STAT3 activation and oncogenesis in lymphoma. Cancers (Basel). 2019;12(1):19. DOI: 10.3390/cancers12010019.Zhu F., Wang K.B., Rui L. STAT3 activation and oncogenesis in lymphoma. Cancers (Basel). 2019;12(1):19. DOI: 10.3390/cancers12010019.Sommer V.H., Clemmensen O.J., Nielsen O. et al. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia. 2004;18(7):1288-1295. DOI: 10.1038/sj.leu.2403385.Sommer V.H., Clemmensen O.J., Nielsen O. et al. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia. 2004;18(7):1288-1295. DOI: 10.1038/sj.leu.2403385.Sibbesen N.A., Kopp K.L., Litvinov I.V. et al. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget. 2015;6(24):2055520569. DOI: 10.18632/oncotarget.4111.Sibbesen N.A., Kopp K.L., Litvinov I.V. et al. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget. 2015;6(24):2055520569. DOI: 10.18632/oncotarget.4111.Rendón-Serna N., Correa-Londoño L.A., Velásquez-Lopera M.M., Bermudez-Muñoz M. Cell signaling in cutaneous T-cell lymphoma microenvironment: promising targets for molecular-specifi c treatment // Int. J. Dermatol. 2021;60(12):1462-1480. DOI: 10.1111/ijd.15451.Rendón-Serna N., Correa-Londoño L.A., Velásquez-Lopera M.M., Bermudez-Muñoz M. Cell signaling in cutaneous T-cell lymphoma microenvironment: promising targets for molecular-specifi c treatment // Int. J. Dermatol. 2021;60(12):1462-1480. DOI: 10.1111/ijd.15451.Sun Z., Yao X., Ding X. et al. MicroRNAs and their signaling pathway in mycosis fungoides. Medicine (Baltimore). 2022;101(25):e29248. DOI: 10.1097/MD.0000000000029248.Sun Z., Yao X., Ding X. et al. MicroRNAs and their signaling pathway in mycosis fungoides. Medicine (Baltimore). 2022;101(25):e29248. DOI: 10.1097/MD.0000000000029248.Solé C., Arnaiz E., Lawrie C.H. MicroRNAs as biomarkers of B-cell lymphoma. Biomark. Insights. 2018;13:1177271918806840. DOI: 10.1177/1177271918806840.Solé C., Arnaiz E., Lawrie C.H. MicroRNAs as biomarkers of B-cell lymphoma. Biomark. Insights. 2018;13:1177271918806840. DOI: 10.1177/1177271918806840.Talaat I.M., Abdelmaksoud R.E., Guimei M. et al. Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients. PLoS One. 2019;14(10):e0224305. DOI: 10.1371/journal.pone.0224305.Talaat I.M., Abdelmaksoud R.E., Guimei M. et al. Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients. PLoS One. 2019;14(10):e0224305. DOI: 10.1371/journal.pone.0224305.Sørensen S.T., Litman T., Gluud M. et al. miRNA signature in early-stage mycosis fungoides. Acta Derm. Venereol. 2022;102:adv00785. DOI: 10.2340/actadv. v102.628.Sørensen S.T., Litman T., Gluud M. et al. miRNA signature in early-stage mycosis fungoides. Acta Derm. Venereol. 2022;102:adv00785. DOI: 10.2340/actadv. v102.628.Shen X., Wang B., Li K. et al. MicroRNA signatures in diagnosis and prognosis of cutaneous T-cell lymphoma. J. Invest. Dermatol. 2018;138(9):2024-2032. DOI: 10.1016/j.jid.2018.03.1500.Shen X., Wang B., Li K. et al. MicroRNA signatures in diagnosis and prognosis of cutaneous T-cell lymphoma. J. Invest. Dermatol. 2018;138(9):2024-2032. DOI: 10.1016/j.jid.2018.03.1500.

The authors declare that there are no conflicts of interest present.