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Vol. 24, Art. 85 (pp. 1237-1257)    |    2023       

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The role of myc/8q24 gene aberrations in the genetic diagnosis of mantle cell lymphoma

Kleina E.1, Voloshin S.1,2, Semenova N.1, Linnikov S.1, Nemscveridze N.1, Bakai M1, Smirnova A.1, Lazareva N.1, Kariagina E.3, Uspenskaia O.4, Ziuzgin I.5, Bessmeltsev S.1, Sidorkevich S.1, Martynkevich I.1

1 Russian Research Institute of Hematology and Transfusiology, Federal Medical and Biological Agency, Russian Federation, Saint-Petersburg
2 Kirov SM Military Medical Academy, Russian Federation, Saint-Petersburg
3 St. Petersburg State budgetary medical institution of health care ?City Hospital No.15?, Russian Federation, Saint-Petersburg
4 State budgetary medical institution Leningrad Regional Clinical Hospital, Russian Federation, Saint-Petersburg
5 ?The N.N. Petrov National Medicine Research Institute of oncology? Ministry of Health of Russia, Russian Federation, Saint-Petersburg

Brief summary

Mantle cell lymphoma (MCL) is a special type of aggressive B-cell non-Hodgkin's lymphomas, accounting for approximately 3-10% of all lymphomas. The detection of a highly specific translocation t(11;14)(q13;q32), which leads to overexpression of the cyclin D1 and dysregulation of the cell cycle, plays a leading role in the cyto- and molecular-cytogenic diagnosis of MCL. In addition to the translocation t(11;14)(q13;q32), which is the primary event of MCL lymphomogenesis, secondary genetic aberrations involving the MYC/8q24 and TP53/17p13 genes are often detected, which determine the pathomorphological characteristics of the tumor clone, as well as the progressive clinical course of MCL. The proto-oncogenic protein MYC, encoded by the MYC/8q24 gene, is the most important transcription factor that regulates the expression of 10-15% of the genes in the human genome and one of the most frequently deregulated oncogenes in malignant neoplasms. Despite the fact that MYC/8q24 gene rearrangement is a diagnostic genetic aberration in patients with Burkitt's lymphoma, in recent years it has been found that MYC/8q24 changes can also occur in other lymphomas, including MCL, causing an unfavorable prognosis with low overall survival (OS) and disease-free survival (DFS). In our study, conducted in 117 patients with MCL, we analyzed the frequency of occurrence and the impact on OS and DFS of changes in the MYC/8q24 gene. In addition, much attention was paid to the consideration of the high-risk MCL group, ?double-hit? MCL, the study of which has been of particular interest in recent years. Aim. To determine the causes and prognostic impact on overall and disease-free survival of MYC/8q24 gene aberrations in 117 patients with MCL and identify a group of patients with a ?double-hit? MCL. Materials and methods. The results of standard cytogenetic and FISH studies of 117 patients diagnosed with MCL are presented. Karyotyping was performed on G-banded metaphase plates obtained from bone marrow or peripheral blood cells. Translocation t(11;14)(q13;q22), aberrations involving TP53/17p13, MYC/8q24 genes were detected by FISH study using locus-specific DNA probes. Results. The conducted study on our sample of patients revealed the heterogeneity of MYC/8q24 gene aberrations and their association with a decrease in the duration of OS, DFS, as well as an unfavorable prognostic effect on the clinical characteristics of the course of the tumor process. Conclusion. Genetic diagnosis of MCL using FISH study to detect aberrations of the MYC/8q24 gene helps to detect high-risk MCL patients, ?double-hit? MCL characterized by changes in the MYC/8q24 gene, translocation t(11;14)(q13;q32) and multiple chromosomal abnormalities.


Key words

Mantle cell lymphoma, double-hit mantle cell lymphoma, genetic aberrations, overall survival, disease-free survival

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