sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.15372/SSMJ20190515sibmed-284Research ArticleКЛИНИЧЕСКАЯ МЕДИЦИНАCLINICAL MEDICINEОЦЕНКА ПРОГНОСТИЧЕСКОГО ЗНАЧЕНИЯ ЭКСПРЕССИИ pSTAT3 ПРИ ДИФФУЗНОЙ В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЕ НА РОССИЙСКОЙ ВЫБОРКЕ ПАЦИЕНТОВPROGNOSTIC VALUE OF pSTAT3 EXPRESSION IN DIFFUSIVE B-LARGE CELL LYMPHOMA IN THE RUSSIAN PATIENT SAMPLEВанееваЕ. В.VaneevaE. V.

6100027, г. Киров, ул. Красноармейская, 72

6100027, Kirov, Krasnoarmeyskaya str., 72

vaneeva.elena.vic@mail.ruhttps://orcid.org/0000-0003-2054-2870РосинВ. А.RosinV. A.

к.м.н., 

6100027, г. Киров, ул. Красноармейская, 72

candidate of medical sciences

6100027, Kirov, Krasnoarmeyskaya str., 72

rosin@niigpk.ruhttps://orcid.org/0000-0001-8688-1344ДьяконовД. А.DyakonovD. A.

к.м.н.,

6100027, г. Киров, ул. Красноармейская, 72

candidate of medical sciences

6100027, Kirov, Krasnoarmeyskaya str., 72

dyakonov@niigpk.ruСамаринаС. В.SamarinaS. V.

6100027, г. Киров, ул. Красноармейская, 72

6100027, Kirov, Krasnoarmeyskaya str., 72

samarina@niigpk.ruРыловА. В.RylovA. V.

д.м.н.

6100027, г. Киров, ул. Красноармейская, 72

doctor of medical sciences

6100027, Kirov, Krasnoarmeyskaya str., 72

Кировский НИИ гематологии и переливания крови ФМБА РоссииРоссияKirov Research Institute of Hematology and Blood Transfusion of FMBA of RussiaRussian Federation201903112019395125133Copyright © Ванеева Е.В., Росин В.А., Дьяконов Д.А., Самарина С.В., Рылов А.В., 20192019Ванеева Е.В., Росин В.А., Дьяконов Д.А., Самарина С.В., Рылов А.В.Vaneeva E.V., Rosin V.A., Dyakonov D.A., Samarina S.V., Rylov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/284

Цель исследования – оценить прогностическое значение экспрессии pSTAT3 при диффузной В-крупноклеточной лимфоме (ДВККЛ) на российской выборке пациентов. Материал и методы. Ретроспективно оценены результаты лабораторного обследования 50 пациентов с впервые диагностированной диффузной B-крупноклеточной лимфомой, проходивших лечение в клинике Кировского НИИ гематологии и переливания крови ФМБА России с 2014 по 2017 г. С помощью иммуногистохимического и морфометрического методов определено относительное количество экспрессирующих pSTAT3 опухолевых клеток. Проанализирована взаимосвязь различного уровня экспрессии маркера с клинико-лабораторными показателями, оценены отдаленные результаты терапии больных. Результаты и их обсуждение. Гиперэкспрессия белка pSTAT3 ассоциирована с non-GCB подтипом заболевания, продвинутой стадией, возрастом пациентов 60 лет и более, а также с меньшей частотой достижения полных ремиссий при ДВККЛ. Больные с высокой степенью экспрессии маркера в опухолевых клетках имели более низкие показатели общей и беспрогрессивной выживаемости. Выявлено, что исследуемый маркер обладает хорошей предсказательной способностью, но не является независимым фактором прогноза при ДВККЛ. Заключение. Уровень экспрессии pSTAT3 является информативным фактором, позволяющим прогнозировать ответ на стандартную терапию при ДВККЛ, и может быть полезен для идентификации пациентов, нуждающихся в индивидуализации лечебной тактики при этом заболевании.

The aim of the study was to evaluate the prognostic value of pSTAT3 expression in diffuse B-large cell lymphoma (DLBCL) in a Russian sample of patients. Material and methods. Retrospectively, the results of an examination of 50 patients with newly diagnosed DLBCL in the period from 2014 to 2017 were evaluated. Using immunohistochemical and morphometric methods, the relative number of tumor cells expressing pSTAT3 was determined. The relationship of various levels of marker expression with clinical and laboratory parameters was analyzed, and long-term results of patient therapy were evaluated. Results and discussion. The overexpression of pSTAT3 protein is associated with a non-GCB subtype of the disease, an advanced stage, the patients of 60 years and older age, as well as with a lower frequency of achieving complete remissions with DLBCL. Patients with a high degree of marker expression in tumor cells had lower rates of overall (OS) and progressive survival (PFS). It was revealed that the marker under study has good predictive ability, but is not an independent prognosis factor for DLBCL. Conclusions. The level of expression of pSTAT3 is an informative factor that allows predicting the response to standard therapy for diffuse B-large cell lymphoma. The indicated marker may be useful for identifying patients who need individualization of therapeutic tactics for this disease.

диффузная В-крупноклеточная лимфомаpSTAT3экспрессиявыживаемостьGCBnon-GCBIPIdiffuse large B-cell lymphomapSTAT3expressionsurvivalGCBnon-GCBIPIReferencesВалиев Т.Т., Ковригина А.М., Попа А.В., Левашов А.С., Менткевич Г.Л. Современные возможности диагностики и лечения диффузной В-крупноклеточной лимфомы у детей и взрослых (обзор литературы). Соврем. онкология. 2015; (3): 30–41.Valiev T.T., Kovrigina A.M., Popa A.V., Levashov A.S., Mentkevich G.L. Modern possibilities of diagnostics and treatment of diffuse large b-cell lymphoma in children and adults (literature review). Sovremennaya onkologiya = Journal of Modern Oncology. 2015; (3): 30–41. [In Russian].Дьяконов Д.А., Росин В.А., Ванеева Е.В., Самарина С.В. Способ морфометрической оценки прогноза течения диффузной В-крупноклеточной лимфомы по содержанию STAT3 опухолевых клеток в лимфатических узлах. Пат. 2694838 РФ; Опубл. 17.07.2019.Dyakonov D.A, Rosin V.A., Vaneeva E.V., Samarina S.V. A method of morphometric assessment of the prognosis of diffuse B-large cell lymphoma by the content of STAT3 tumor cells in lymph nodes. Patent 2694838 RF; Published 17.07. 2019. [In Russian].Поддубная И.В. Диффузная В-клеточная крупноклеточная лимфома. В кн.: Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Ред. И.В. Поддубная, В.Г. Савченко. М.: Буки Веди, 2018. 58–65.Poddubnaya I.V. Diffuse large B-cell lymphoma. In: Russian clinical recommendations on diagnostics and treatment of lymphoproliferative disorders. Eds. I.V. Poddubnaya, V.G. Savchenko. Moscow: Buki Vedi, 2018. 58–65. [In Russian].Расторгуев С.М., Королева Д.А., Булыгина Е.С. Цыганкова С.В., Гончаров Н.Г., Нарайкин О.С., Габеева Н.Г., Звонков Е.Е., Недолужко А.В. Клиническое и прогностическое значение молекулярных маркеров диффузной В-крупноклеточной лимфомы. Клин. онкогематология. 2019; 12 (1): 95–100. doi: 10.21320/2500-2139-2019-12-1-95-100.Rastorguev S.M., Koroleva D.A., Bulygina E.S., Tsygankova S.V., Goncharov N.G., Naraykin O.S., Gabeeva N.G., Zvonkov E.E., Nedoluzhko A.V. Clinical and prognostic value of molecular markers of diffuse large B-cell lymphoma. Klinicheskaya onkogematologiya = Clinical Oncohematology. 2019; 12 (1): 95–100. [In Russian]. doi: 10.21320/2500-2139-2019-12-1-95-100.Шапошников А.В., Комарьков И.Ф., Лебедева Л.А., Шидловский Ю.В. Строение сигнального пути JAK/STAT и его взаимосвязь с аппаратом транскрипции. Молекул. биология. 2013; 47 (3): 388–397. doi: 10.7868/s0026898413030130.Shaposhnikov A.V., Komar’kov I.F., Lebedeva L.A., Shidlovskii Yu.V. Molecular components of JAK/STAT signaling pathway and its interaction with transcription machinery. Mol. Biol. 2013; 47 (3): 343–351. doi: 10.7868/s0026898413030130.Aaronson D.S., Horvath C.M. A road map for those who don’t know JAK-STAT. Science. 2002; 296 (5573): 1653–1655. doi: 10.1126/science.1071545.Aaronson D.S., Horvath C.M. A road map for those who don’t know JAK-STAT. Science. 2002; 296 (5573): 1653–1655. doi: 10.1126/science.1071545.Adida C., Haioun C., Gaulard P., Lepage E., Morel P., Briere J., Dombret H., Reyes F., Diebold J., Gisselbrecht C., Salles G., Altieri D.C., Molina T.J. Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood. 2000; 96 (5): 1921–1925.Adida C., Haioun C., Gaulard P., Lepage E., Morel P., Briere J., Dombret H., Reyes F., Diebold J., Gisselbrecht C., Salles G., Altieri D.C., Molina T.J. Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood. 2000; 96 (5): 1921–1925.Alizadeh A.A., Eisen M.B., Davis R.E. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000. 403: 503–511. doi: 10.1038/35000501.Alizadeh A.A., Eisen M.B., Davis R.E. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000. 403: 503–511. doi: 10.1038/35000501.Bastion Y., Blay J.Y., Divine M., Brice P., Bordessoule D., Sebban C., Blanc M., Tilly H., Lederlin P., Deconinck E., Salles B., Dumontet C., Briere J., Coiffier B. Elderly patients with aggressive non-Hodgkin’s lymphoma: disease presentation, response to treatment, and survival – a Groupe d’Etude des Lymphomes de l’Adulte study on 453 patients older than 69 years. J. Clin. Oncol. 1997; 15 (8): 2945–2953. doi: 10.1200/JCO.1997.15.8.2945.Bastion Y., Blay J.Y., Divine M., Brice P., Bordessoule D., Sebban C., Blanc M., Tilly H., Lederlin P., Deconinck E., Salles B., Dumontet C., Briere J., Coiffier B. Elderly patients with aggressive non-Hodgkin’s lymphoma: disease presentation, response to treatment, and survival – a Groupe d’Etude des Lymphomes de l’Adulte study on 453 patients older than 69 years. J. Clin. Oncol. 1997; 15 (8): 2945–2953. doi: 10.1200/JCO.1997.15.8.2945.Сabattini E., Pileri S.A., Dirnhofer S., Went P., Ascani S., Marafioti T., Tzankov A., Leoncini L., Falini B., Zinzani P.L. Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology. 2002; 41 (6): 482–509. doi: 10.1046/j.1365-2559.2002.01538.x.Сabattini E., Pileri S.A., Dirnhofer S., Went P., Ascani S., Marafioti T., Tzankov A., Leoncini L., Falini B., Zinzani P.L. Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology. 2002; 41 (6): 482–509. doi: 10.1046/j.1365-2559.2002.01538.x.Darnell J.E. Validating Stat3 in cancer therapy. Nat. Med. 2005; 11: 595–596. doi: 10.1038/nm0605-595.Darnell J.E. Validating Stat3 in cancer therapy. Nat. Med. 2005; 11: 595–596. doi: 10.1038/nm0605-595.Ding B.B., Yu J.J., Yu R.Y., Mendez L.M., Shaknovich R., Zhang Y., Cattoretti G., Ye B.H. Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood. 2008; 111 (3): 1515–1523. doi: 10.1182/blood-2007-04-08773.doi: 10.1182/blood-2007-04-087734.Ding B.B., Yu J.J., Yu R.Y., Mendez L.M., Shaknovich R., Zhang Y., Cattoretti G., Ye B.H. Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood. 2008; 111 (3): 1515–1523. doi: 10.1182/blood-2007-04-08773.doi: 10.1182/blood-2007-04-087734.Gomez H., Mas L., Casanova L., Pen D.L., Santillana S., Valdivia S., Otero J., Rodriguez W., Carracedo C., Vallejos C. Elderly patients with aggressive non-Hodgkin’s lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: identification of two age subgroups with differing hematologic toxicity. J. Clin. Oncol. 1998; 16 (7): 2352–2358. doi: 10.1200/JCO.1998.16.7.2352.Gomez H., Mas L., Casanova L., Pen D.L., Santillana S., Valdivia S., Otero J., Rodriguez W., Carracedo C., Vallejos C. Elderly patients with aggressive non-Hodgkin’s lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: identification of two age subgroups with differing hematologic toxicity. J. Clin. Oncol. 1998; 16 (7): 2352–2358. doi: 10.1200/JCO.1998.16.7.2352.Hans C.P., Weisenburger D.D., Greiner T.C., Gascoyne R.D., Delabie J., Ott G., Muller Hermelink H.K., Campo E., Braziel R.M., Jaffe E.S., Pan Z., Farinha P., Smith L.M., Falini B., Banham A.H., Rosenwald A., Staudt L.M., Connors J.M., Armitage J.O., Chan W.C. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103 (1): 275–282. doi: 10.1182/blood-2003-05-1545.Hans C.P., Weisenburger D.D., Greiner T.C., Gascoyne R.D., Delabie J., Ott G., Muller Hermelink H.K., Campo E., Braziel R.M., Jaffe E.S., Pan Z., Farinha P., Smith L.M., Falini B., Banham A.H., Rosenwald A., Staudt L.M., Connors J.M., Armitage J.O., Chan W.C. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103 (1): 275–282. doi: 10.1182/blood-2003-05-1545.Huang X., Meng B., Iqbal J., Ding B.B., Perry A.M., Cao W., Smith L.M., Bi C., Jiang C., Greiner T.C., Weisenburger D.D., Rimsza L., Rosenwald A., Ott G., Delabie J., Campo E., Braziel R.M., Gascoyne R.D., Cook J.R., Tubbs R.R., Jaffe E.S., Armitage J.O., Vose J.M., Staudt L.M., McKeithan T.W., Chan W.C., Ye B.H., Fu K. Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP. J. Clin. Oncol. 2013; 31 (36): 4520-4528. doi: 10.1200/JCO.2012.45.6004Huang X., Meng B., Iqbal J., Ding B.B., Perry A.M., Cao W., Smith L.M., Bi C., Jiang C., Greiner T.C., Weisenburger D.D., Rimsza L., Rosenwald A., Ott G., Delabie J., Campo E., Braziel R.M., Gascoyne R.D., Cook J.R., Tubbs R.R., Jaffe E.S., Armitage J.O., Vose J.M., Staudt L.M., McKeithan T.W., Chan W.C., Ye B.H., Fu K. Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP. J. Clin. Oncol. 2013; 31 (36): 4520-4528. doi: 10.1200/JCO.2012.45.6004Lam L.T., Wright G., Davis R.E. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma. Blood. 2008; 111: 3701–3713. doi: 10.1182/blood-2007-09-111948.Lam L.T., Wright G., Davis R.E. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma. Blood. 2008; 111: 3701–3713. doi: 10.1182/blood-2007-09-111948.Lin S., Yujun L., Xiaoming X., Wenwen R. Expression and significance of leptin receptor, p-STAT3 and p-AKT in diffuse large B-cell lymphoma. Acta Histochem. 2014; 116: 126–130. doi: 10.1016/j.acthis.2013.06.003.Lin S., Yujun L., Xiaoming X., Wenwen R. Expression and significance of leptin receptor, p-STAT3 and p-AKT in diffuse large B-cell lymphoma. Acta Histochem. 2014; 116: 126–130. doi: 10.1016/j.acthis.2013.06.003.Liu H., Zhu L., Sun C., Xie W., Qian W., Ye X. Clinical significance and prognostic value of STAT3 expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy. Int. J. Clin. Exp. Med. 2016; 9 (6): 9356–9364.Liu H., Zhu L., Sun C., Xie W., Qian W., Ye X. Clinical significance and prognostic value of STAT3 expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy. Int. J. Clin. Exp. Med. 2016; 9 (6): 9356–9364.Meyer P.N., Fu K., Greiner T.C., Smith L.M., Delabie J., Gascoyne R.D., Ott G., Rosenwald A., Braziel R.M., Campo E., Vose J.M., Lenz G., Staudt L.M., Chan W.C., Weisenburger D.D. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J. Clin. Oncol. 2011; 29 (2): 200–207. doi: 10.1200/JCO.2010.30.0368.Meyer P.N., Fu K., Greiner T.C., Smith L.M., Delabie J., Gascoyne R.D., Ott G., Rosenwald A., Braziel R.M., Campo E., Vose J.M., Lenz G., Staudt L.M., Chan W.C., Weisenburger D.D. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J. Clin. Oncol. 2011; 29 (2): 200–207. doi: 10.1200/JCO.2010.30.0368.Morgensztern D., Lossos I.S. Molecular prognostic factors in diffuse large B-cell lymphoma. Curr. Treat. Options Oncol. 2005; 6 (4): 269–277.Morgensztern D., Lossos I.S. Molecular prognostic factors in diffuse large B-cell lymphoma. Curr. Treat. Options Oncol. 2005; 6 (4): 269–277.Ok C.Y., Chen J., Xu-Monette Z.Y., Tzankov A., Manyam G.C., Li L., Visco C., Montes-Moreno S., Dybkaer K., Chiu A., Orazi A., Zu Y., Bhagat G., Richards K.L., Hsi E.D., Choi W.W., van Krieken J.H., Huh J., Zhao X., Ponzoni M., Ferreri A.J., Bertoni F., Farnen J.P., Moller M.B., Piris M.A., Winter J.N., Medeiros L.J., Young K.H. Clinical implications of phosphorylated STAT3 expression in de novo diffuse large B-cell lymphoma. Clin. Cancer Res. 2014; 20 (19): 5113–5123. doi: 10.1158/1078-0432.CCR-14-0683.Ok C.Y., Chen J., Xu-Monette Z.Y., Tzankov A., Manyam G.C., Li L., Visco C., Montes-Moreno S., Dybkaer K., Chiu A., Orazi A., Zu Y., Bhagat G., Richards K.L., Hsi E.D., Choi W.W., van Krieken J.H., Huh J., Zhao X., Ponzoni M., Ferreri A.J., Bertoni F., Farnen J.P., Moller M.B., Piris M.A., Winter J.N., Medeiros L.J., Young K.H. Clinical implications of phosphorylated STAT3 expression in de novo diffuse large B-cell lymphoma. Clin. Cancer Res. 2014; 20 (19): 5113–5123. doi: 10.1158/1078-0432.CCR-14-0683.Ok C.Y., Chen J., Xu-Monette Z.Y., Tzankov A., Visco C., Chiu A., Orazi A., Zu Y., Bhagat G., Richards K.L., Hsi E.D., Choi W.W., van Krieken J.H., Ponzoni M., Ferreri A.J., Farnen J.P., Moller M.B., Winter J.N., Piris M.A., Medeiros L.J., Young K.H. STAT3 expressions and clinical inplications in de Novo diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013; 122: 365.Ok C.Y., Chen J., Xu-Monette Z.Y., Tzankov A., Visco C., Chiu A., Orazi A., Zu Y., Bhagat G., Richards K.L., Hsi E.D., Choi W.W., van Krieken J.H., Ponzoni M., Ferreri A.J., Farnen J.P., Moller M.B., Winter J.N., Piris M.A., Medeiros L.J., Young K.H. STAT3 expressions and clinical inplications in de Novo diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013; 122: 365.Rawlings J.S., Rosler K.M., Harrison D.A. The JAK/STAT signaling pathway. J. Cell Sci. 2004; 117 (8): 1281–1283. doi: 10.1242/jcs.00963.Rawlings J.S., Rosler K.M., Harrison D.A. The JAK/STAT signaling pathway. J. Cell Sci. 2004; 117 (8): 1281–1283. doi: 10.1242/jcs.00963.Rosenwald A., Wright G., Chan W.C. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002; 346 (25): 1937–1947. doi: 10.1056/NEJMoa012914.Rosenwald A., Wright G., Chan W.C. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002; 346 (25): 1937–1947. doi: 10.1056/NEJMoa012914.Sehn L.H., Gascoyn R.D. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015; 125 (1): 22–32. doi: 10.1182/blood-2014-05-577189.Sehn L.H., Gascoyn R.D. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015; 125 (1): 22–32. doi: 10.1182/blood-2014-05-577189.Shipp M.A., Ross K.N., Tamayo P. Diffuse large B-cell lymphoma outcome prediction by geneexpression profiling and supervised machine learning. Nat. Med. 2002; 8: 68–74. doi: 10.1038/nm0102-68.Shipp M.A., Ross K.N., Tamayo P. Diffuse large B-cell lymphoma outcome prediction by geneexpression profiling and supervised machine learning. Nat. Med. 2002; 8: 68–74. doi: 10.1038/nm0102-68.WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th Edition. Eds. S.H. Swerdlow, E. Campo, N.L. Harris, E.S. Jaffe, S.A. Pileri, H. Stein, J. Thiele. Geneva: WHO Press, 2017. 585 p.WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th Edition. Eds. S.H. Swerdlow, E. Campo, N.L. Harris, E.S. Jaffe, S.A. Pileri, H. Stein, J. Thiele. Geneva: WHO Press, 2017. 585 p.Wu Z.L., Song Y.Q., Shi Y.F., Zhu J. High nuclear expressions of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J. Hematol. Oncol. 2011; 4 (31): 1–6. doi: 10.1186/1756-8722-4-31.Wu Z.L., Song Y.Q., Shi Y.F., Zhu J. High nuclear expressions of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J. Hematol. Oncol. 2011; 4 (31): 1–6. doi: 10.1186/1756-8722-4-31.Yu H., Pardoll D., Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer. 2009; 9 (11): 798–809. doi: 10.1038/nrc2734.Yu H., Pardoll D., Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer. 2009; 9 (11): 798–809. doi: 10.1038/nrc2734.

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