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Registration Number

0216U003553, , 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

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 "

Description

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.

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