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Registration Number

0216U003547, 0113U002317 , R & D reports

Title

Definition of the role of genetic and epigenetic alterations in the genome of somatic cells in the pathogenesis of chronic lymphoproliferative diseases, their diagnostics and clinical significance

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Head

Bebeshko Volodymyr; Minchenko Zhanna,

Registration Date

01-02-2016

Organization

State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine "

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Object of research - biological material 131 patients with multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's malignant lymphoma. The aim - based on the study of DNA methylation pattern in comparison with the status of rearrangment fragments IgVH, spectrum of chromosome aberrations, the main characteristics of the blood genetic systems and stage of the disease to determine the contribution of genetic and epigenetic changes in the somatic cells genome in the mechanisms of chronic lymphoproliferative disorders development and course in patients with chronic lymphoproliferative diseases, including the potential recipients of peripheral stem cells transplantation. Methods - molecular cytogenetic, cytogenetic, immunogenetic, immunological, hematological, culture and statistics. Analysis of molecular cytogenetic analysis of chromosome abnormalities indicates that, for verification of the diagnosis and prognosis of the disease and the choice of optimal treatment strategy the most important are the following molecular cytogenetic markers: t(8;14) - for Burkitt's lymphoma, t(11;14) - for mantle cell lymphoma, t(14;18) - for follicular lymphoma, t(4;14) and t(14;16) - for multiple myeloma. It was indicated that genetic abnormalities in chromosome 12 (trisomy), 13 (deletion of 13q14, 13q34) and 17 (deletion 17p13.1) affect the prognosis of HLPN. Genetic abnormalities in chromosome 12 (trisomy), 13 (deletion of 13q14, 13q34) and 17 (deletion 17p13.1) are the most important cytogenetic abnormalities for prognosis of the HLPD course. Concentration of IL-6 and TNF-alfa in the serum of PB in patients with MM were significantly higher than in healthy individuals. Significant decrease in the concentration of TNF-alfa was recorded in patients achieved CR or PR. The highest concentrations of TNF-alfa and IL-6 were detected in MM patients with resistance to chemotherapy. The number of CFU-F in bone marrow in patients with MM depends on the form and stage of disease. The algorithm of monitoring for recipients of autologous HSCT was improved: at the stage of disease verification is necessary to perform molecular and cytogenetic analysis of chromosome abnormalities - del17p, del13q, t(4;14), t(11;14) and their combinations, that have predictive value for response to therapy. In the late post-transplant period, repeated molecular cytogenetic examination of patients is an important. Repeated molecular cytogenetic examination should be performed in the late post-transplant period. The presence of alleles HLA-B*27, HLA-B*40, HLA-DRB1*04; HLA-DQB1*0302 indicates a high risk of refractoriness to HD CHT. Patient's genotype of with the specificities HLA-A*01, HLA-B*14, HLA-DQA1*0103 predicts a positive outcome. The worst response to the VAD therapy was registered in patients with A (II) phenotype in phase III MM. Positive response on transplantation is associated with HLA-C*06 and HLA-DQA1*0101. According to the processed data of clinical and genetic testing a set of criteria for predicting the course of the disease based on the genetic and epigenetic status of the somatic cells genome of patients with HLPD was designed.

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Балан Валентина Володимирівна
Дмитренко Олена Олександрівна
Мішаріна Жанна Анатоліївна
Сітько Валентина Віталіївна
Хоменко Віктор Іванович
Шляхтиченко Тетяна Юріївна

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2020-04-02