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MicroRNA as a molecular predictor of hematological toxicity during chemotherapy in patients with Hodgkin lymphoma

https://doi.org/10.31549/2542-1174-2024-8-2-54-66

Abstract

Introduction. A great success of modern oncohematology is the achievement of remission with timely initiation of chemotherapy regimen in 80–85% of patients with Hodgkin lymphoma (HL). However, the problem of the occurrence of severe therapy-related toxic complications of specifi c therapy in this group of patients remains relevant. MicroRNAs (miRs) aff ect the maturation and diff erentiation of mesenchymal cells, including bone marrow cells, can play a key role in the activity of normal hematopoiesis and hematopoietic tumors, and also regulate the activity of gene metabolism of anticancer drugs.

Aim. To determine the relationship between the miRNA expression in tumor biopsy samples of lymph nodes in patients with HL at the onset of the disease and the development of hematological toxicity during chemotherapy.

Materials and methods. In accordance with the Common Terminology Criteria for Adverse Events v5.0, hematological toxicity was assessed in 40 patients with HL treated with the ABVD (n = 13) and BEACOPP (n = 27) chemotherapy regimens. The real-time polymerase chain reaction was used to determine the expression of 20 miRNAs in tumor biopsy samples of lymph nodes in all patients with HL before chemotherapy and in histological preparations of patients (n = 40) with reactive lymphadenopathy (RL) as a control group.

Results. Toxic myelosuppression increased from the 1st to the 6th cycle of chemotherapy in patients treated with both the ABVD and BEACOPP regimens (p < 0.05). At the same time, grade 3–4 hematological toxicity in patients with HL treated with the BEACOPP regimen occurred 3 times more often than in patients with ABVD (p < 0.05), which indicates greater toxicity of the BEACOPP regimen. Overexpression of let-7c-5p, miR-185-5p and miR-128-3p positively correlates with the development of moderate and severe anemia (p < 0.05) in patients with HL after chemotherapy, suppressing the processes of maturation and diff erentiation of bone marrow cells, as well as activating their apoptosis.

Conclusion. Determining the miRNA expression as molecular genetic predictors of the development of chemotherapy-related organ toxicity in patients with HL will help achieve appropriate treatment results, reducing the risks of adverse eff ects and maintaining a high quality of life for patients after chemotherapy.

About the Authors

Y. Y. Shebunyaeva
Novosibirsk State Medical University; State Novosibirsk Regional Clinical Hospital
Russian Federation

Yana Y. Shebunyaeva – Post-graduate student, Department of Therapy, Hematology and Transfusiology; Hematologist, Department of Hematology with Aseptic Wards

52, Krasny prosp., Novosibirsk, 630091



Y. A. Veryaskina
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Yulia A. Veryaskina – Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Genetics, Institute of Molecular and Cellular Biology; Researcher, Laboratory of Genetic Engineering, Institute of Cytology and Genetics

Novosibirsk



S. E. Titov
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Sergey E. Titov – Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Genetics, Institute of Molecular and Cellular Biology

Novosibirsk



M. S. Voytko
Novosibirsk State Medical University
Russian Federation

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

Novosibirsk



I. F. Zhimulev
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Igor F. Zhimulev – Dr. Sci. (Biol.), Head, Laboratory of Molecular Cytogenetics, Institute of Molecular and Cellular Biology

Novosibirsk



T. I. Pospelova
Novosibirsk State Medical University
Russian Federation

Tatyana I. Pospelova – Dr. Sci. (Med.), Professor, Head, Department of Therapy, Hematology and Transfusiology

Novosibirsk



References

1. Demina E.A (2021). Guidelines for Hodgkin Lymphoma Treatment. Мoscow: Remedium, 96 p. (In Russ.)

2. Danilenko А.А. Late side eff ects of radio- and chemo-radiotherapy of primary patients with Hodgkin lymphoma: Cand. Sci. (Med.) thesis. Obninsk, 2017. (In Russ.)

3. Poddubnaya I.V., Savchenko V.G. (eds.) (2016). Russian Clinical Guidelines for the Diagnosis and Treatment of Lymphoproliferative diseases / Russian Oncohematology Society; Russian Medical Academy of Postgraduate Education; National Society of Hematology. Moscow, 324 p. (In Russ.)

4. Huang Z., Wang M., Liu L. et al. Transcriptional repression of CYP3A4 by increased miR-200a-3p and miR-150-5p promotes steatosis in vitro. Front. Genet. 2019;10:484. DOI: 10.3389/fgene.2019.00484. PMID: 31191607. PMCID: PMC6546834.

5. Yu D., Green B., Tolleson W.H. et al. MicroRNA hsamiR-29a-3p modulates CYP2C19 in human liver cells. Biochem. Pharmacol. 2015;98(1):215-223. DOI: 10.1016/j.bcp.2015.08.094. PMID: 26296572. PMCID: PMC5673105.

6. Yu D., Green B., Marrone A. et al. Suppression of CYP2C9 by microRNA hsa-miR-128-3p in human liver cells and association with hepatocellular carcinoma. Sci. Rep. 2015;5:8534. DOI: 10.1038/srep08534. PMID: 25704921. PMCID: PMC4336941.

7. Singh D., Kashyap A., Pandey R.V., Saini K.S. Novel advances in cytochrome P450 research. Drug Discov. Today. 2011;16(17-18):793-799. DOI: 10.1016/j.drudis.2011.08.003. PMID: 21864709.

8. Pang B., Mao H., Wang J., Yang W. MiR-185-5p suppresses acute myeloid leukemia by inhibiting GPX1. Microvasc. Res. 2022;140:104296. DOI: 10.1016/j.mvr.2021.104296. PMID: 34863990.

9. Zhang W., Zhu Y., Chen J. et al. Mechanisms of miR-128-3p in inhibiting osteoblast diff erentiation from bone marrow-derived mesenchymal stromal cells. Mol. Med. Rep. 2020;22(6):5041-5052. DOI: 10.3892/mmr.2020.11600. PMID: 33174052. PMCID: PMC7646956.

10. Umezu T., Tsuneyama K., Kanekura K. et al. Comprehensive analysis of liver and blood miRNA in precancerous conditions. Sci. Rep. 2020;10(1):21766. DOI: 10.1038/s41598-020-78500-1. PMID: 33303811. PMCID: PMC7728755.

11. Yan Z., Guo Y., Wang Y. et al. MicroRNA profi les of BMSCs induced into osteoblasts with osteoinductive medium. Exp. Ther. Med. 2018;15(3):2589-2596. DOI: 10.3892/etm.2018.5723. PMID: 29456662. PMCID: PMC5795604.

12. Di Lisio L., Sánchez-Beato M., Gómez-López G. et al. MicroRNA signatures in B-cell lymphomas. Blood Cancer J. 2012;2:e57.

13. Kobilov O.R. Substantiation and principles of correction af hematological toxicity of polychemotherapy of malignant tumors (review of literature). Herald of Science and Education. 2019;17(71):6872. DOI: 10.24411/2312-8089-2019-11703. (In Russ.)

14. Skoetz N., Will A., Monsef I. et al. Comparison of fi rstline chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst. Rev. 2017;5(5):CD007941. DOI: 10.1002/14651858.CD007941.pub3. PMID: 28541603; PMCID: PMC6481581.

15. Filatova L.V., Plotnikova A.A., Gershanovich M.L., Semiglazova T.Yu. The efficacy and toxicity of programs MOPP, ABVD, BEACOPP-baseline in primary Hodgkin’s lymphoma patients with a poor prognosis. Problems in Oncology. 2013;59(2):59- 65. (In Russ.)

16. Ono R., Yoshioka Y., Furukawa Y. et al. Novel hepatotoxicity biomarkers of extracellular vesicle (EV)- associated miRNAs induced by CCl4. Toxicol. Rep. 2020;7:685-692. DOI: 10.1016/j.toxrep.2020.05.002. PMID: 32528856; PMCID: PMC7283084.

17. O’Brien J., Hayder H., Zayed Y., Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. (Lausanne). 2018;9:402. DOI: 10.3389/fendo.2018.00402 PMID: 30123182. PMCID: PMC6085463.

18. Jang J.H., Lee T.J. The role of microRNAs in cell death pathways. Yeungnam Univ. J. Med. 2021;38(2):107- 117. DOI: 10.12701/yujm.2020.00836. PMID: 33435638 PMCID: PMC8016624

19. Calin G.A., Sevignani C., Dumitru C.D. et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA. 2004;101(9):2999-3004. DOI: 10.1073/pnas.0307323101. PMID: 14973191. PMCID: PMC365734.

20. Navarro A., Gaya A., Martinez A. et al. MicroRNA expression profi ling in classic Нodgkin lymphoma. Blood. 2008;111(5):2825–2832. DOI: 10.1182/blood-2007-06-096784. PMID: 18089852.

21. Paydas S., Acikalin A., Ergin M. et al. Micro-RNA (miRNA) profi le in Hodgkin lymphoma: association between clinical and pathological variables. Med. Oncol. 2016;33(4):34. DOI: 10.1007/s12032-016-0749-5. PMID: 26951445.

22. Özdemir Z.C., Düzenli Kar Y., Bör Ö. Whole blood miR-210, miR-122, miR-223 expression levels and their relationship with iron status parameters and hypercoagulability indices in children with iron defi ciency anemia. J. Pediatr. Hematol. Oncol. 2021;43(3):e328-e335. DOI: 10.1097/MPH.0000000000002127. PMID: 33710119.

23. Li N., Liu L., Liu Y. et al. miR-144-3p suppresses osteogenic diff erentiation of BMSCs from patients with aplastic anemia through repression of TET2. Mol. Ther. Nucleic. Acids. 2020;19:619-626. DOI: 10.1016/j.omtn.2019.12.017. PMID: 31945725. PMCID: PMC6965517.

24. Yu Z., Chen C., Xiao Y. et al. Abnormal miR-214/A20 expression might play a role in T cell activation in patients with aplastic anemia. Blood Sci. 2020;2(3):100-105. DOI: 10.1097/BS9.0000000000000053. PMID: 35402824. PMCID: PMC8974947.


Review

For citations:


Shebunyaeva Y.Y., Veryaskina Y.A., Titov S.E., Voytko M.S., Zhimulev I.F., Pospelova T.I. MicroRNA as a molecular predictor of hematological toxicity during chemotherapy in patients with Hodgkin lymphoma. Journal of Siberian Medical Sciences. 2024;8(2):54-66. (In Russ.) https://doi.org/10.31549/2542-1174-2024-8-2-54-66

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