MicroRNA as a molecular predictor of hematological toxicity during chemotherapy in patients with Hodgkin lymphoma
Authors:   Novosibirsk State Medical University, Novosibirsk, Russia, Shebunyaeva Y.Y. ,   State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia, Veryaskina Y.A. ,   Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Titov S.Е. ,   Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Voytko М.S. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Zhimulev I.F. ,   Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, Pospelova T.I. ,   Novosibirsk State Medical University, Novosibirsk, Russia
Published: September 2024

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 specific therapy in this group of patients remains relevant. Micro¬RNAs (miRs) affect the maturation and differentiation 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 differentiation 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 effects and maintaining a high quality of life for patients after chemotherapy.