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Registration Number

0215U003221, 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; Minchtnko Zhanna,

Registration Date

21-01-2015

Organization

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

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Object of study - biological material of 107 patients with multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's malignant lymphoma. Aim - to study the epigenetic status of cell cycle regulation genes and of cytokine production genes and to analyze rearrangement fragments of immunoglobulin heavy chains genes in patients with chronic lymphoproliferative disorders. Methods - molecular cytogenetic, cytogenetic, immunogenetic, immunological, hematological, cultural and statistics. Results. The abnormalities of chromosome 17 in the locus of TR 53 gene were found in 36 of 107 (34%) CLPD patients as a result of molecular cytogenetic analysis of bone marrow, lymph nodes and peripheral blood. Clonal deletion of the TP 53 gene was revealed more often. Hiperaneuployidiyi of chromosome 17 were registered in 14% of patients with CLPD. 49 (46%) patients had not changes of genetic structures. Translocations t (4;14), t(11;14) of genes FGFR3 and CCND1 were not found in B-CLL patients. IGH aneuploidy were identified in 4 patients of 10. Translocation t(11;14) was registered in 4.3% of MM patients. A retrospective study of 17 samples of paraffinized biopsy material from lymph nodes of DBCL patients and three samples - of Burkitt's lymphoma patients showed that MYC rearrangements were registered for Burkitt's lymphoma in two of the three patients. Translocation t(8;14) was found in two of seventeen patients with DKVL. Aneuploidy of chromosomes 8 and 14 was registered in six of twenty patients. The need to identify differential prognostic markers of the disease, including chromosomal rearrangements, was confirmed. It was shown that the presence in a HLA-genotype alleles HLA-A*24; HLA-B*52; HLA-C*06; DRB1*08, HLA-DQB1*05 and HLA-DQB1*06 is a factors of genetic susceptibility to the MM. Allele HLA-A*01 has a protective function. The selection of the primers with optimum number of CG dinucleotides located mainly in promoter areas of these genes was made. Methylation pattern of genes CCND1, TNF-alpha and IGHJ1 in genomic DNA of patients satisfied the reference DNA, changes were not detected. It was proved that before chemotherapy in patients with MM concentration of IL-6 and TNF-? in a peripheral blood serum significantly exceeded one in healthy individuals. The highest concentrations of TNF-? and IL-6 were identified in MM patients with resistance to chemotherapy. The number of CFU-F in multiple myeloma petients depended on the form and stage of disease.

Product Description

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

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2020-04-02