Defects in the tumor suppressor gene TP53 are known to be important in chronic lymphocytic leukemia (CLL) and TP53 inactivation is associated with a particularly aggressive form of the disease. The single nucleotide polymorphism in the TP53 gene at codon 72 (rsl042522), results in amino acid substitution influencing apoptotic potential of TP53 protein. The aim of the study was to evaluate the association of the TP53 codon 72 polymorphism and incidence of TP53 mutations in CLL patients. 261 CLL samples were analyzed by polymerase chain reaction and direct sequencing for TP53 mutations and single nucleotide polymorphism. The 72Pro/Pro genotype was associated with an increased incidence of TP53 mutations in previously treated patients (OR = 2,503; 95 % CI 1,142 - 5,487; p = 0,001). Conclusion: this study revealed that the TP53 codon 72 polymorphism may be used as a risk factor for incidence of TP53 mutations in CLL.

The aim of this study was to examine the JAK2 V617F, the G1691A allele of factor V, and the G2021OA prothrombin gene mutation status, and their predictive value for thrombosis in patients with Ph-negative myeloproliferative neoplasms (MPN) in Ukraine, with special emphasize to patient exposed to ionizing radiation due to the Chernobyl accident. There were198 patients with Ph-negative MPN included in the study. Of these, 45 patients had experienced radiation exposure due to the Chernobyl accident. The JAK2 V617F mutation, the G1691A of factor V and the G20210A of prothrombin were detected by allele-specific polymerase chain reaction. The polycythemia vera and essential thrombocythemia patients in unexposed group and Chernobyl patients were comparable in terms of the JAK2 V617F mutation prevalence with the frequency of anomaly corresponding well to the published data on unselectcd cases of these types of Ph-negative MPN. The JAK2 V617F mutation was less common on the border of statistical significance (p = 0,08) in Chernobyl primary myelofibrosis (PMF) patients than in non-exposed patients. JAK2 V617F positive patients had higher level of leukocytes (p = 0,03), hemoglobin (p = 0,04) and splenomegaly (p = 0,04) than those without mutation. The JAK2 V617F mutation was strong predictor for thrombosis in essential thrombocytemia patients (relative risk = 3,1, 95 % CI = 1,7 - 16,4, p = 0,03). In PMF, the association with thrombosis was found for the G1691A allele of factor V (p = 0,03). The risk of thrombosis associated with the inherited thrombophilia in PMF patients was 7,0-foid (95 % CI = 1,41 - 33,1, p = 0,03) higher than in polycythemia vera patients. The inherited thrombophilia increased risk of thrombotic complication 5,4-fold (95 % CI = 1,41 - 18,17, p = 0,01) in overall cohort of Ph-negative myeloproliferative neoplasms patients. This trend continued in Chernobyl patients (p = 0,02), but not in unexposed cases. Conclusions: our findings confirm previous results of other studies reporting that the JAK2 V617F mutation significantly and independently influences on a disease phenotype in Ph-negative MPN. The inherited thrombophilia is important risk factors of the thrombosis development in overall cohort primary myelofibrosis patients, and especially in disease developed following radiation exposure.

Aim - to evaluate real-time polymerase chain reaction (PCR) assay system for detection of NOTCH1 c.7541_754delCT mutation in chronic lymphocytic leukemia (CLL) patients. A total of 325 CLL patients were included in the study. Screening for NOTCH1 c.7544_7545delCT was performed using conventional PCR-based amplification refractory mutation system (ARMS) method. All 33 samples harboring c.7544_7545delCT allele and 5 negative cases as control were submitted to real-time PCR. Specificity and sensitivity of two PCR techniques were comparable. NOTCH1 c.7544_7545delCT mutation was found by ARMS in 10,1 % of CLL patients, which is consistent with the data of other studies. However, the results of ARMS PCR in a minority of cases (2,15 %) were doubtful and required reinvestigation. Real-time PCR, being less time-consuming, showed advantage in the assessment of the amplification's specificity (using the melting curve analysis). It also allows the quantitative assessment of NOTCHl-nrnt&teA clone. Conclusion: NOTCH1 c.7544_7545delCT mutation resulting in removal of the C-terminal PEST domain, deregulation of NOTCH 1-dependent signaling pathways, has negative influence on prognosis of CLL and efficiency of therapy with anti-CD20 monoclonal antibodies. Real-time PCR allows the fast and reliable detection of c.7544_7545delCT mutation and can be used for the screening of this molecular lesion in CLL patients.

Previous analyses in a cohort of Chornobyl cleanup workers revealed significantly increased radiation-related risk for all leukemia types, including chronic lymphocytic leukemia (CLL). Numerous investigations emphasized the significance of genetic susceptibility to the radiation carcinogenesis. The aim of the work was to study the distribution of TP53 single nucleotide polymorphisms (SNPs) in CLL patients exposed to ionizing radiation (IR) due to Chornobyl nuclear power plant accident and estimate their impact on disease development. The TP53 exonic and intronic SNPs were analyzed in 236 CLL patients by polymerase chain reaction and direct sequencing. The main group included 106 IR exposed CLL patients and the control group was composed of 130 IR non-exposed CLL patients. Nineteen TP53 SNPs were found in the observed CLL cohort. No significant differences were found between the main and the control groups, but increased frequencies of T/T rsl2947788 + G/G rsl2951053 homozygotes and rs 146340390 C/T variants were found among IR-exposed CLL patients compared with healthy Europeans (data from the 1000 Genomes Project). Rare nucleotide substitution rsl46340390 (c.665C>>T) was found only in the main group. These features were primarily typical for the most affected group of IR-exposed patients, namely, cleanup workers engaged in emergency works in the nd quarter of 1986. Conclusion: These preliminary findings don't contradict the assumption on possible influence of IR on CLL development via the p53-dependent pathway. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Індекс рубрикатора НБУВ: Р411.022.3

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Лімфатичні лейкози

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р411.022.3

Рубрики:

Лімфатичні лейкози

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ