title: NOTCH1 mutations in chronic lymphocytic leukemia patients sufferers of Chornobyl NPP accident.
abstract: Objective - to estimate the frequency of NOTCH1 mutations in chronic lymphocytic leukemia (CLL) patients, suffer ers of Chornobyl NPP accident, for elucidation of their impact in development of radiation associated forms of dis ease.
  
  
  METHODS
  NOTCH1 mutations were determined by polymerase chain reaction followed by direct sequencing in 201 previously untreated patients with CLL of B cell origin: 88 CLL patients, sufferers of the Chornobyl NPP accident, and 113 CLL patients of the control group.
  
  
  RESULTS
  Mutations of NOTCH1 were found in 13.4 % of observed patients, mostly in cases with unmutated heavy chain variable region (IGHV) genes (p = 0.001). Patients of the two groups were comparable by gender, age, stage at diagnosis, and mutational status of IGHV genes. But, the frequency of NOTCH1 mutations in the main group appeared to be lower in comparison with the control group (6.8 % vs 18.6 %; p = 0.015). Furthermore, if in the con trol group the number of NOTCH1 mutations increased in patients requiring first treatment compared with patients at diagnosis (p = 0.012), in the main group such differencies were non significant (p = 0.317). When clinical data of all observed groups of patients were analyzed, the presence of NOTCH1 mutations was associated with more advanced stage of disease, higher initial WBC count, bulky disease, short time to treatment period and progression free survival.
  
  
  CONCLUSIONS
  Our data confirmed negative prognostic value of NOTCH1 mutations, but suggested to minimal impact of NOCTH1 mutations in CLL development under exposure to ionizing radiation.
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, 53, Melnikov str., Kyiv, 04050, Ukraine.
authors.forename: N I
authors.initials: NI
authors.lastname: Bilous
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, 53, Melnikov str., Kyiv, 04050, Ukraine.
authors.forename: I V
authors.initials: IV
authors.lastname: Abramenko
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, 53, Melnikov str., Kyiv, 04050, Ukraine.
authors.forename: A A
authors.initials: AA
authors.lastname: Chumak
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, 53, Melnikov str., Kyiv, 04050, Ukraine.
authors.forename: I S
authors.initials: IS
authors.lastname: Djagil
authors.affiliation: State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, 53, Melnikov str., Kyiv, 04050, Ukraine.
authors.forename: Z V
authors.initials: ZV
authors.lastname: Martina
keywords: Chornobyl NPP accident; NOTCH1 mutations; chronic lymphocytic leukemia; ionizing radiation