OVEREXPRESSION OF STAT4 - A POSSIBLE DIAGNOSTIC MARKER OF EARLY STAGES OF MYCOSIS FUNGOIDES

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background. Mycosis fungoides (MF) is the most common disease among the cutaneous T-cell lymphomas (85-90%). The accuracy of the diagnosis of MF, which is confirmed only by clinical, histological and immunohistochemical signs, is 50-75%. The aim of the study was to investigate genetic markers (FOXP3, STAT4, IL-12B) for early diagnosis of mycosis fungoides. Material and methods. A study involving 42 patients with MF and plaque parapsoriasis (PP) treated at the Dermatology Department of I.M. Sechenov First Moscow State Medical University and National Medical Hematology Research Сenter, was performed. The analysis of gene expression FOXP3, STAT4, IL-12B was carried out by TaqMan Real time-PCR. The objects of the study were lesional skin samples of patients. A group with MF consisted of 29 patients, a group with PP consisted of 13 patients, a control group included 10 healthy volunteers. Results. The study revealed that the level of STAT4 gene expression showed a significant (9 times) increase in the mRNA expression of STAT4 transcripts in patients with MF (166) compared with patients with PP (17.9; p < 0.05) and 553 times - with healthy volunteers (0.3; p < 0.05). There was also a statistically significant predominance of the level of mRNA expression of STAT4 transcripts in patients with spotted and plaque stages of MF (180; 318) compared with patients with PP (17.9; p < 0.05) and healthy volunteers (0.3; p < 0.05), as well as a sharp decrease in patients with erythrodermic form of MF (7.19). For early diagnosis of MF the level of expression of mRNA transcripts STAT4 is of great importance. Inclusion of STAT4 in the list of diagnostic features increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%.

Full Text

Restricted Access

About the authors

O. Yu Olisova

V.A. Rakhmanov Department of Skin and Veneral Diseases of I.M. Sechenov First Moscow State Medical University

119991, Moscow, Russian Federation

Ekaterina V. Grekova

V.A. Rakhmanov Department of Skin and Veneral Diseases of I.M. Sechenov First Moscow State Medical University

Email: grekova_kate@mail.ru
postgraduate at the Department of Skin and Veneral Diseases n.a. V.A. Rakhmanov of I.M. Sechenov First Moscow State Medical University, 119991, Moscow, Russian Federation 119991, Moscow, Russian Federation

L. G Gorenkova

National Medical Hematology Research Сenter

Moscow, 125167, Russian Federation

E. A Alekseeva

Laboratory of medical genetics, Institute of molecular medicine of I.M. Sechenov First Moscow State Medical University; Laboratory of epigenetics of Research Centre of Medical Genetics

119991, Moscow, Russian Federation; 115522, Moscow, Russian Federation

D. V Zaletayev

Laboratory of medical genetics, Institute of molecular medicine of I.M. Sechenov First Moscow State Medical University; Laboratory of epigenetics of Research Centre of Medical Genetics

119991, Moscow, Russian Federation; 115522, Moscow, Russian Federation

References

  1. Willemze R., Jaffe E.S., Burg G., Cerroni L., Berti E. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105(10): 3768-85.
  2. Rodd A.L., Ververis K., Karagiannis T.C. Current and emerging therapeutics for cutaneous T-cell lymphoma: histone deacetylase inhibitors. Lymphoma. 2012; 2012: 1-10. http://dx.doi.org/10.1155/2012/290685. Available at: https://www.hindawi.com/journals/lymph/2012/290685/
  3. Olsen E.A., Whittaker S., Kim Y. H., Duvic M., Prince H. M. Clinical end points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J. Clin. Oncol. 2011; 29(18): 2598-607.
  4. Белоусова И.Э. Федеральные клинические рекомендации по ведению больных лимфомами кожи. М.; 2015
  5. Willerslev-Olsen A., Litvinov I.V., Fredholm S.M., Petersen D.L. IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides. Cell Cycle. 2014; 13(8): 1306-12
  6. Сыдиков А.А., Заславский Д.В., Зайцев В.С., Насыров Р.А. Иммуногистохимические критерии диагностики мелкобляшечного парапсориаза, крупнобляшечного парапсориза и грибовидного микоза. Современные проблемы науки и образования. 2013; (6): 568.
  7. Братцева Е.В., Ротанов С.В. Современные подходы к диагностике грибовидного микоза. Вестник дерматологии и венерологии. 2010; (6): 16-22.
  8. Bernier C., Nguyen J.M., Quereux G., Renault J.J., Bureau B., Dreno B. CD13 and TCR clone: markers of early mycosis fungoides. Acta Derm. Venereol. 2007; 87(2): 155-9.
  9. Berger C.L., Hanlon D., Kanada D., Dhodapkar M., Lombillo V. The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells. Blood. 2002; 99(8): 2929-39.
  10. Жуков А.С., Белоусова И.Э., Самцов А.В. Foxp3+ Т-лимфоциты в патогенезе грибовидного микоза. Вестник дерматологии и венерологии. 2014; (5): 68-72
  11. Krejsgaard T., Odum N., Geisler C., Wasik M.A., Woetmann A. Regulatory T cells and immunodeficiency in mycosis fungoides and Sezary syndrome. Leukemia 2012; 26(3): 424-32
  12. Жуков А.С., Белоусова И.Э., Самцов А.В. Иммунологические и молекулярно-генетические механизмы развития грибовидного микоза. Вестник дерматологии и венерологии. 2015; (4): 42-50
  13. Lasek W., Zagozdzon R., Jakobisiak M. Interleukin 12: still a promising candidate for tumor immunotherapy? Cancer Immunol. Immunother. 2014; 63(5): 419-35.
  14. Netchiporouk E., Litvinov I.V., Moreau L., Gilbert M., Sasseville D., Duvic M. Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression. Cell Cycle. 2014; 13(21): 3331-5.
  15. Sommer V.H., Clemmensen O.J., Nielsen O., Wasik M., Lovato P., Brender C., et al. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia. 2004; 18(7): 1288-95.
  16. Nishikomori R., Usui T., Wu C.Y., Morinobu A., O’Shea J.J., Strober W. Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling. J. Immunol. 2002; 169(8): 4388-98.
  17. Litvinov I., Cordeiro B., Fredholm S., Odum N., Zargham H., Huang Y. Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines. Cell Cycle. 2014; 13(18): 2975-82.
  18. Johnson V.E., Vonderheid E.C. Hess A.D., Eischen C.M., McGirt L.Y. Genetic markers associated with progression in early mycosis fungoides. J. Eur. Acad. Dermatol. Venerol. 2014; 28(11): 1431-5.

Statistics

Views

Abstract: 110

Dimensions

Article Metrics

Metrics Loading ...

PlumX


Copyright (c) 2018 Eco-Vector



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies