ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 15 No. 2 (2022), LYMPHOID TUMORS
Vol. 15 No. 2 (2022)
LYMPHOID TUMORS

Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

Published 01.04.2022
Elena Viktorovna Vaneeva
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027
V.A. Rosin
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027
D.A. Dyakonov
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027
S.V. Samarina
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027
I.V. Paramonov
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027
PDF_2022-15-2-140-147 (Russian)

Keywords

diffuse large B-cell lymphoma
pAKT1 and pSyk expression
overall survival
progression-free survival

How to Cite

Vaneeva E.V., Rosin V.A., Dyakonov D.A., Samarina S.V., Paramonov I.V. Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma. Clinical Oncohematology. 2022;(2):140–147. doi:10.21320/2500-2139-2022-15-2-140-147.
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver AMA ГОСТ

Download Citation

Endnote/Zotero/Mendeley (RIS) BibTeX

Statistics

Annotation views: 3
PDF_2022-15-2-140-147 (Russian) downloads: 1

Keywords

Abstract

Aim. To assess the prognostic value of pAKT1 and рSyk expression in DLBCL.

Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cut-off of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher’s exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test).

Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49–10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54–7.30; p = 0.002).

Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

PDF_2022-15-2-140-147 (Russian)

References

  1. Bahar T, Chowdhury ZZ, Rahman S, et al. Clinicopathological Correlation with Outcome of Diffuse Large B Cell Lymphoma: Experience in a Specialized Cancer Care Centre in Bangladesh. J Medicine. 2021;22(1):3–6. doi: 3329/jom.v22i1.51383.
  2. Самарина С.В., Лучинин А.С., Минаева Н.В. и др. Иммуногистохимический подтип и параметры международного прогностического индекса в новой модели прогноза диффузной B-крупноклеточной лимфомы. Клиническая онкогематология. 2019;12(4):385–90. doi: 21320/2500-2139-2019-12-4-385-390.
  3. [Samarina SV, Luchinin AS, Minaeva NV, et al. Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(4):385–90. doi: 10.21320/2500-2139-2019-12-4-385-390. (In Russ)]
  4. Mondello P, Mian M, Frontline treatment of diffuse large B-cell lymphoma: Beyond R‐ Hematol Oncol. 2019;37(4):333–44. doi: 10.1002/hon.2613.
  5. Song JL, Wei XL, Zhang YK, et al. The prognostic value of the international prognostic index, the national comprehensive cancer network IPI and the age-adjusted IPI in diffuse large B cell lymphoma. Zhonghua Xue Ye Xue Za Zhi. 2018;39(9):739–44. doi: 10.3760/cma.j.issn.0253-2727.2018.09.007.
  6. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11(1):12–23. doi: 10.1038/nrclinonc.2013.197.
  7. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11. doi: 10.1038/35000501.
  8. Расторгуев С.М., Королева Д.А., Булыгина Е.С. и др. Клиническое и прогностическое значение молекулярных маркеров диффузной В-крупноклеточной лимфомы. Клиническая онкогематология. 2019;12(1):95–100. doi: 10.21320/2500-2139-2019-12-1-95-100.
  9. [Rastorguev SM, Koroleva DA, Boulygina ES, et al. Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(1):95–100. doi: 10.21320/2500-2139-2019-12-1-95-100. (In Russ)]
  10. Miao Yi, Medeiros LJ, Xu-Monette ZY, et al. Dysregulation of Cell Survival in Diffuse Large B Cell Lymphoma: Mechanisms and Therapeutic Targets. Front Oncol. 2019;9:107. doi: 3389/fonc.2019.00107.
  11. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2014;94(3):193–205. doi: 10.1111/ejh.12427.
  12. Никитин E.A. Передача сигнала через B-клеточный рецептор: механизмы и ингибиторы. Клиническая онкогематология. 2014;7(3):251–63.
  13. [Nikitin EA. B­Cell Receptor Signaling Pathway: Mechanisms and Inhibitors. Klinicheskaya onkogematologiya. 2014;7(3):251–63. (In Russ)]
  14. Wossning T, Herzog S, Kohler F, et al. Deregulated Syk inhibits differentiation and induces growth factor-independent proliferation of pre-B cells. J Exp Med. 2006;203(13):2829–40. doi: 10.1084/jem.20060967.
  15. Kumar А, Rajendran V, Sethumadhavan R, Purohit R. AKT Kinase Pathway: A Leading Target in Cancer Research. ScientificWorldJournal. 2013; 2013:756134. doi: 10.1155/2013/756134.
  16. Ванеева Е.В., Росин В.А., Дьяконов Д.А. и др. Значение экспрессии pAKT1 при диффузной В-крупноклеточной лимфоме. Бюллетень сибирской медицины. 2021;3:6–13.
  17. [Vaneeva EV, Rosin VA, D’yakonov DA, et al. Significance of pAKT1 expression in diffuse large B-cell lymphoma. Byulleten’ sibirskoi meditsiny. 2021;3:6–13. (In Russ)]
  18. Karmali R, Gordon LI. Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy. Curr Treat Options Oncol. 2017;18(2):11. doi: 10.1007/s11864-017-0449-1.
  19. Wang X, Cao X, Sun R, et al. Clinical Significance of PTEN Deletion, Mutation, and Loss of PTEN Expression in De Novo Diffuse Large B-Cell Lymphoma. Neoplasia. 2018;20(6):574–93. doi: 10.1016/j.neo.2018.03.002.
  20. Wang J, Xu-Monette ZY, Jabbar KJ, et al. AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma. Am J Pathol. 2017;187(8):1700–16. doi: 10.1016/j.ajpath.2017.04.009.
  21. Hong JY, Hong ME, Choi MK, et al. The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases. Ann Oncol. 2014;25(1):182–8. doi: 10.1093/annonc/mdt530.
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Copyright (c) 2022 Clinical Oncohematology