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Information × Registration Number 0216U003553, 0114U002846 , R & D reports Title To 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 popup.stage_title Head Chumak Anatoliy Andriyovych, Доктор медичних наук Registration Date 01-02-2016 Organization State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine " popup.description2 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 control group). Methods: polymerase chain reaction, direct sequencing of reaction products, clinical, statistical. The main results: the frequencies of TP53 (11.3% and 12.7%) and SF3B1 (10% and 11.5%) gene mutations wert similar in the main and in the control groups. The frequency of NOTCH1 mutations appeared to be lower in IR-exposed CLL patients (6.7% vs 17.7%; p=0.012). The co-existence of TP53 and SF3B1 mutations was higher in the main group (4.4% vs 0.81% in the control group; p=0.001). This feature was found in patients, irradiated in the first period after Chornobyl NPP accisent (clean-up workers of iodine period and evacuees). In main group we found 2 identical cases (1.88%) of rare polymorphism rs146340390 of TP53 gene, which frequency is only 0.06% according to literature data. 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). In patients with unmutated IGHV genes and Arg/Arg genotype the development of TP53 and SF3B1 mutations was associated with genotype GG SNP309 of MDM2 (р=0.023), and expression of IGHV3-21 gene (р=0,046). In patients with mutated IGHV genes and Arg/Arg or Arg/Pro genotype the development of TP53 and SF3B1 mutations was associated with expression of IGHV4-59 gene (p=0.001), IGHV3-30 gene (p=0.01), and IGHV3-21 gene, set 2 (p=0.03). The influence of rs1801270 p21 gene's polymorphism on the frequencies of unfavorable mutations in CLL patients was not revealed. Product Description popup.authors Абраменко Ірина Вікторівна Білоус Надія Іванівна Дягіль Ірина Сергіївна popup.nrat_date 2020-04-02 Close