Registration Number
0217U000433,
0114U002846
, R & D reports
Title
t o study the risk of development of prognostic unfavorable genetic lesions in chronic lymphocytic leukemia patients sufferers due to Chornobyl NPP accident depend on p53-associated apoptosis gene polymorphisms
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Head
Chumak Anatoliy Andriyovych, Доктор медичних наук
Registration Date
03-02-2017
Organization
State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine "
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The aim of work - to study the frequency of ТР53 and NOTCH1 gene's mutations in CLL patients depend on radiation factor and gene polymorphisms of p53-depended apoptosis. The object of study: 236 patients with chronic lymphocytic leukemia (CLL), including 106 ionizing radiation (IR) exposed patients due to Chornobyl NPP catastrophe (the main group), and 130 IR non-exposed CLL patients (the group of comparison); 145 persons without oncohematological diseases (the control). Methods: polymerase chain reaction, direct sequencing of reaction products, clinical, statistical. The main results: the following features of the irradiated CLL patients were revealed: increased frequency of homozygous T/T rs12947788 and G/G rs12951053 (p = 0.042), as well as polymorphism rs146340390 of ТР53 gene (p = 0.001) compared to healthy individuals of the European population; decrease in the frequency of NOTCH1 mutations (6.7% against 17.7% in the group of comparison; p = 0,012); increased frequency of the co-existence of TP53 and SF3B1 mutations (4.4 % vs 0.82 % in the group of comparison; p=0.001). These features were typical for CLL patients, irradiated in the first period after Chornobyl NPP accisent (clean-up workers of April-May, 1986 and evacuees). At the same time, the frequencies of TP53 mutations (11,3% and 12.7%) and SF3B1 mutations (10,0% and 11.5%) in the main group and in the group of comparison were similar. It was found that CLL patients with unmutated IGHV genes were risk group for development of NOTCH1 mutations OR = 16.06 (95% СІ 2.14 - 74.10; р=0.001). Carriers of Pro/Pro genotype of rs1042522 TP53 gene, regardless of mutational status of IGHV genes, were risk group for development of TP53 and SF3B1 mutations: OR = 4.889 (95% СІ 1.974 - 12.162; р=0.001). An algorithm for determining the risk of TP53 and/or SF3B1 mutations depending on rs1042522 polymorphism and mutation status of IGHV genes was proposed. A method for revealing of NOTCH1 mutations by real-time PCR, which allows to more accurately predict the duration of progression-free survival of patients was developed. Some features of CLL in carriers of GG genotype by SNP309 of MDM2 gene were established. The negative prognostic significance of rs1800372 of TP53 gene was revealed. Publications: 8 papers, draft guidelines, the patent application.
Product Description
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Абраменко Ірина Вікторівна
Білоус Надія Іванівна
Дягіль Ірина Сергіївна
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2020-04-02
