ABSTRACT
UNLABELLED: 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. CONCLUSION: 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.
